Publications by authors named "Yun Tang"

393 Publications

An Experience-Sampling Study on Academic Stressors and Cyberloafing in College Students: The Moderating Role of Trait Self-Control.

Front Psychol 2021 4;12:514252. Epub 2021 May 4.

School of Psychology, Central China Normal University, Wuhan, China.

Student cyberloafing is a relatively new educational phenomenon and is getting to be an outstanding issue that educators have to face. It is necessary to find out important factors that aggravate cyberloafing. Using an experience sampling method, this study examined the relationship between academic stressors and cyberloafing. Once a week for five consecutive weeks (T1-T5), 134 undergraduate students assessed the extent of academic stressors and cyberloafing of that week through an electronic questionnaire. Additionally, participants completed a trait self-control scale at Time 2. Results of two-level regression analysis showed that academic stressors were negatively associated with cyberloafing at the within-person level (i.e., week-to-week changes), but not at the between-person level. Furthermore, this relationship pattern was only observed in students with low trait self-control, while those with high trait self-control were less likely to cyberloaf regardless of academic stressors. These findings suggest that cyberloafing can fluctuate over periods, especially for individuals who lack self-control. Future research should consider cyberloafing from a dynamic perspective of individual-context interaction. Several practical implications are also discussed.
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http://dx.doi.org/10.3389/fpsyg.2021.514252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314437PMC
May 2021

High-Temperature and Large-Polarization Ferroelectric with Second Harmonic Generation Response in a Novel Crown Ether Clathrate.

Chemistry 2021 Jul 28. Epub 2021 Jul 28.

JiangXi University of Science and Technology, Faculty of Materials Metallurgy and Chemistry, CHINA.

Molecular ferroelectrics of high-temperature reversible phase-transition are very rare and have attracted increasing attention in recent years. In this paper, we have successfully synthesized a novel high-temperature host-guest inclusion ferroelectric: [ (C 6 H 5 NF 3 ) (18-crown-6)][BF 4 ] (1) , which shows a pair of reversible peaks at 348 K (heating) and 331 K (cooling) with a heat hysteresis about 17 K by differential scanning calorimetry (DSC) measurements, indicating that 1 undergoes a reversible structural phase transition. The variable-temperature PXRD and temperature-dependent dielectric measurements further prove the phase-transition behavior of 1 . The second harmonic response demonstrates that 1 belongs to a non-centrosymmetric space group at room temperature and is a good nonlinear optical material. Meanwhile, 1 shows a wide optical band gap of about 4.43 eV in semiconducting property and is chiefly contributed by C, H and O atoms of the crystals. In particular, the ferroelectric measurements of 1 exhibit a typical polarization-electric hysteresis loop with large spontaneous polarization ( P s ) of about 4.06 μC/ cm 2 . This finding offers an alternative pathway for designing new ferroelectric-dielectric and nonlinear optical materials and related physical properties in organic- inorganic and other hybrid crystals.
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http://dx.doi.org/10.1002/chem.202101707DOI Listing
July 2021

Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches.

Chin Med 2021 Jul 23;16(1):59. Epub 2021 Jul 23.

Laboratory of Molecular Modeling and Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

Background: The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods.

Methods: Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein-protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed.

Results: 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway.

Conclusions: This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.
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http://dx.doi.org/10.1186/s13020-021-00473-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306236PMC
July 2021

Analyzing the gonadal transcriptome of the frog Hoplobatrachus rugulosus to identify genes involved in sex development.

BMC Genomics 2021 Jul 19;22(1):552. Epub 2021 Jul 19.

Laboratory of Amphibian Diversity Investigation, College of Ecology, Lishui University, Lishui, 323000, Zhejiang, People's Republic of China.

Background: The tiger frog (Hoplobatrachus rugulosus) is listed as a national Class II protected species in China. In the context of global warming, the sex ratio of amphibians will be affected, and the development of the population will be limited. Therefore, considering the potential for a decrease in the number of amphibians, studying sex evolution and molecular regulation of gonadal development in H. rugulosus, phenomenon that are currently unclear, is of great significance.

Results: Here, H. rugulosus was used to explore the mechanisms regulating gonadal development in amphibians. Illumina HiSeq 3000 was used to sequence the gonadal transcriptome of male and female H. rugulosus at two growth stages to identify genes related to gonadal development and analyze expression differences in the gonads. This analysis indicated that cyp17α, hsd3β, hsd11β1, cyp19α, and hsd17β12 perform vital functions in sex development in amphibians. Specifically, the expression of cyp3α, cyp17α, hsd3β, hsd11β1, sox2, sox9, sox30, soat, cyp19α, hsd17β12, and hspα1s was correlated with gonadal development and differentiation in H. rugulosus, as determined using the quantitative reverse transcriptase-polymerase chain reaction.

Conclusion: Significant differences were found in the gonadal gene expression levels in H. rugulosus of both sexes, and we identified a steroid hormone synthesis pathway in this species and analyzed related gene expression, but the changes during sex differentiation were still unclear. To our knowledge, this report presents the first analysis of the H. rugulosus gonadal transcriptome and lays the foundation for future research.
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http://dx.doi.org/10.1186/s12864-021-07879-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290591PMC
July 2021

In Silico Prediction of CYP2C8 Inhibition with Machine-Learning Methods.

Chem Res Toxicol 2021 Jul 13. Epub 2021 Jul 13.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Cytochrome P450 2C8 (CYP2C8) is a major drug-metabolizing enzyme in humans and is responsible for the metabolism of ∼5% drugs in clinical use. Thus, inhibition of CYP2C8, which causes potential adverse drug events, cannot be neglected. The in vitro drug interaction studies guidelines for industry issued by the FDA also point out that it needs to be determined whether investigated drugs are CYP2C8 inhibitors before clinical trials. However, current studies mainly focus on predicting the inhibitors of other major P450 enzymes, and the importance of CYP2C8 inhibition has been overlooked. Therefore, there is a need to develop models for identifying potential CYP2C8 inhibition. In this study, in silico classification models for predicting CYP2C8 inhibition were built by five machine-learning methods combined with nine molecular fingerprints. The performance of the models built was evaluated by test and external validation sets. The best model had AUC values of 0.85 and 0.90 for the test and external validation sets, respectively. The applicability domain was analyzed based on the molecular similarity and exhibited an impact on the improvement of prediction accuracy. Furthermore, several representative privileged substructures such as 1-benzo[]imidazole, 1-phenyl-1-pyrazole, and quinoline were identified by information gain and substructure frequency analysis. Overall, our results would be helpful for the prediction of CYP2C8 inhibition.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00078DOI Listing
July 2021

Effect of preoperative nutrition therapy type and duration on short-time outcomes in gastric cancer patient with gastric outlet obstruction.

Chin J Cancer Res 2021 Apr;33(2):232-242

Department of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.

Objective: To avoid perioperative complications caused malnutrition, nutrition therapy is necessary in gastric outlet obstruction (GOO) patients. Compared to parenteral nutrition (PN), enteral nutrition (EN) is associated with many advantages. This study aimed to investigate whether preoperative EN has beneficial clinical effects compared to preoperative PN in gastric cancer patients with GOO undergoing surgery.

Methods: According to the methods of preoperative nutrition therapy, 143 patients were divided into EN group (n=42) and PN group (n=101) between January 2013 and December 2017 at the Chinese People's Liberation Army General Hospital. Multiple logistic regression models were used to assess the association between the methods of preoperative nutrition therapy and postoperative day of flatus passage. The generalized additive model and two-piecewise linear regression model were used to calculate the inflection point of the preoperative nutritional therapy time on the postoperative day of flatus passage in the PN group.

Results: EN shortened the postoperative day of flatus passage in gastric cancer patients with GOO, which is a protective factor, especially in patients who underwent non-radical operations and the postoperative day of flatus passage reduced when the preoperative PN therapy was up to 3 d and a longer PN therapy (>3 d) did not accelerate the postoperative recovery of gastrointestinal functions.

Conclusions: Preoperative EN therapy would benefit gastric cancer patients with GOO by accelerating postoperative recovery. For patients with absolute obstruction, no more than 3-day PN therapy is recommended if patients can tolerate general anesthesia and surgery.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.02.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181873PMC
April 2021

Integrated signaling system under endoplasmic reticulum stress in eukaryotic microorganisms.

Appl Microbiol Biotechnol 2021 Jun 9;105(12):4805-4818. Epub 2021 Jun 9.

Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421000, Hunan, China.

The endoplasmic reticulum (ER) is a multifunctional organelle, which is crucial for correct folding and assembly of secretory and transmembrane proteins. Perturbations of ER function can cause ER stress. ER stress can activate the unfolded protein response (UPR) to cope with the accumulation of misfolded proteins and protein toxicity. UPR is a coordination system that regulates transcription and translation, leading to the recovery of ER homeostasis or cell death. However, cells have an integrated signaling system to cope with ER stress, which helps cells to restore and balance their ER function. The main components of this system are ER-associated degradation (ERAD), autophagy, hypoxia signaling, and mitochondrial biogenesis. If the balance cannot be restored, the imbalance will lead to cell death or apoptosis, or even to a series of diseases. In this review, a series of activities to restore the homeostasis of cells during ER stress are discussed. KEY POINTS: • Endoplasmic reticulum (ER) plays a key role in the biological process of cells. • Perturbations of ER function can cause ER stress, including the ER overload response (EOR), sterol-regulated cascade reaction, and the UPR. • Cells have an integrated signaling system (ERAD, autophagy, hypoxia signaling, and mitochondrial biogenesis) to cope with the adverse impact caused by ER stress.
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http://dx.doi.org/10.1007/s00253-021-11380-1DOI Listing
June 2021

Single-parameter-tuned synthesis for shape-controlled gold nanocrystals stimulated by iron carbonyl.

J Colloid Interface Sci 2021 May 29;601:773-781. Epub 2021 May 29.

Department of Chemistry, Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433, PR China. Electronic address:

Shape-controlled synthesis is essential for functional nanomaterials, allowing deeper insights intothe relationship between the structures and the catalytic properties. Synthesis of nanocrystals with particular morphologies are usually studied independently among various synthetic methods, those underline that different surface capping ligands or shape-directing agents bring about disparate shapes. However, a single quantitative parameter method is still lacking to realize precise control of well-defined morphology nanocrystals, especially anisotropic structures, which is essential to understanding the growth process of nanocrystals. Herein, we proposed a single-parameter-tuned synthesis strategy for preparation of shape-controlled gold nanocrystals by regulating the amount of iron carbonyl, by which we produced highly monodisperse Au nanocrystals with various shapes in organic phase including nanoplates (diameter of 16.02 ± 1.13 nm and thickness of 5.35 ± 0.58 nm), nanorods (length of 37.53 ± 3.73 nm and width of 5.26 ± 0.37 nm) and nanospheres (diameter of 8.26 ± 0.38 nm). The single-parameter-tuned method reveals the dual roles of iron carbonyl for controlling the shapes of gold nanocrystals including reductant and oxidative etchant and empowers versatility in synthetic methodology for other noble metals. Moreover, catalytic activity shifting in shapes of nanocrystals was revealed based on the reduction of 4-nitrophenol, showing that the as-synthesized Au nanoplates displayed the enhanced catalytic performance with the lowest activation energy. Our work provides a brand-new pathway for shape-controlled synthesis of noble-metal nanocrystals and has a strong practical value in application fields.
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http://dx.doi.org/10.1016/j.jcis.2021.05.114DOI Listing
May 2021

Quantized doping of CdS quantum dots with twelve gold atoms.

Chem Commun (Camb) 2021 Jun;57(52):6448-6451

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Laboratory of Advanced Materials, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Fudan University, Shanghai 200433, China.

Through a bottom-up strategy, CdS quantum dots (QDs) doped with 12 gold atoms in each nanocrystal (NC) were prepared by cation exchange reactions. The (Au12) dopants inside the CdS matrix were directly observed using Cs-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images and quantitatively confirmed using the inductively coupled plasma atomic emission spectroscopy (ICP-AES) data. With a photoluminescence quantum yield (PLQY) of 37.5%, the as-prepared (Au12)@CdS QDs emitted light at 635 nm. Due to the injection of excited electrons from the lowest unoccupied molecular orbital (LUMO) of dopants to the conduction band (CB) of CdS, multiple fine peaks were observed in the photoluminescence excitation (PLE) spectra. By using clusters as starting materials, we demonstrate a universal approach for the precise tailoring of dopants and provide a pathway for band energy engineering of doped QDs.
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http://dx.doi.org/10.1039/d1cc02460dDOI Listing
June 2021

Comparison of short-term outcomes and quality of life in totally laparoscopic distal gastrectomy and totally robotic distal gastrectomy for clinical stage I-III gastric cancer: study protocol for a multi-institutional randomised clinical trial.

BMJ Open 2021 05 25;11(5):e043535. Epub 2021 May 25.

Department of General Surgery & Institute of General Surgery, Chinese PLA General Hospital, Beijing, China

Introduction: Laparoscopic distal gastrectomy (LDG) is regarded as a standard treatment for patients with clinical stage I-III gastric cancer. With the popularisation of the robotic system in the 21st century, robotic distal gastrectomy has been increasingly applied, and its potential advantages over LDG have been proved by several studies. Intraperitoneal anastomosis is a hot topic in research as it highlights the superiority of minimally invasive surgery and is safe and feasible. We intend to conduct this randomised clinical trial to focus on short-term outcomes and quality of life (QOL) in totally laparoscopic distal gastrectomy (TLDG) and totally robotic distal gastrectomy (TRDG) for patients with clinical stage I-III gastric cancer.

Methods And Analysis: This study is a prospective, multi-institutional, open-label randomised clinical trial that will recruit 722 patients with a 1:1 ratio (361 patients in the TLDG group and 361 patients in the TRDG group) from eight large-scale gastrointestinal medical centres in China. The primary endpoint is 30-day postoperative morbidity. The secondary endpoints include QOL, 30-day severe postoperative morbidity and mortality, anastomotic-related complication rate, conversion to open surgery rate, intraoperative and postoperative indicators, operative and total costs during hospitalisation, 1-year overall survival and disease-free survival. QOL is determined by the The European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnare-Core 30 and Stomach22 (EORTC QLQ-C30 and STO22) questionnaires which are completed before surgery and 1, 3, 6 months, and 1 year after surgery. χ test will be used for the primary endpoint, while analysis of covariance will be used to compare the overall changes of QOL between the two groups.

Ethics And Dissemination: This trial was approved by the Ethics Committee of the Chinese PLA General Hospital. The trial's results will be disseminated via peer-reviewed scientific journals and conference presentations.

Trial Registration Number: ChiCTR2000032670.
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http://dx.doi.org/10.1136/bmjopen-2020-043535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154927PMC
May 2021

Discovery of Natural Products Targeting NQO1 via an Approach Combining Network-Based Inference and Identification of Privileged Substructures.

J Chem Inf Model 2021 05 6;61(5):2486-2498. Epub 2021 May 6.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.

NAD(P)H:quinone oxidoreductase 1 (NQO1) has been shown to be a potential therapeutic target for various human diseases, such as cancer and neurodegenerative disorders. Recent advances in computational methods, especially network-based methods, have made it possible to identify novel compounds for a target with high efficiency and low cost. In this study, we designed a workflow combining network-based methods and identification of privileged substructures to discover new compounds targeting NQO1 from a natural product library. According to the prediction results, we purchased 56 compounds for experimental validation. Without the assistance of privileged substructures, 31 compounds (31/56 = 55.4%) showed IC < 100 μM, and 11 compounds (11/56 = 19.6%) showed IC < 10 μM. With the assistance of privileged substructures, the two success rates were increased to 61.8 and 26.5%, respectively. Seven natural products further showed inhibitory activity on NQO1 at the cellular level, which may serve as lead compounds for further development. Moreover, network analysis revealed that osthole may exert anticancer effects against multiple cancer types by inhibiting not only carbonic anhydrases IX and XII but also NQO1. Our workflow and computational methods can be easily applied in other targets and become useful tools in drug discovery and development.
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http://dx.doi.org/10.1021/acs.jcim.1c00260DOI Listing
May 2021

The role of ferroptosis in breast cancer patients: a comprehensive analysis.

Cell Death Discov 2021 May 4;7(1):93. Epub 2021 May 4.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.

Breast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.
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http://dx.doi.org/10.1038/s41420-021-00473-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097021PMC
May 2021

CATMoS: Collaborative Acute Toxicity Modeling Suite.

Environ Health Perspect 2021 Apr 30;129(4):47013. Epub 2021 Apr 30.

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. models built using existing data facilitate rapid acute toxicity predictions without using animals.

Objectives: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 ( value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [ ()], and nontoxic chemicals ().

Methods: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches.

Results: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with results.

Discussion: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495.
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http://dx.doi.org/10.1289/EHP8495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086800PMC
April 2021

Quantitative Nano-amperometric Measurement of Intravesicular Glutamate Content and its Sub-Quantal Release by Living Neurons.

Angew Chem Int Ed Engl 2021 07 9;60(29):15803-15808. Epub 2021 Jun 9.

Sauvage Center for Molecular Sciences, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.

Quantitative measurements of intravesicular glutamate (Glu) and of transient exocytotic release contents directly from individual living neurons are highly desired for understanding the mechanisms (full or sub-quantal release?) of synaptic transmission and plasticity. However, this could not be achieved so far due to the lack of adequate experimental strategies relying on selective and sensitive Glu nanosensors. Herein, we introduce a novel electrochemical Glu nanobiosensor based on a single SiC nanowire that can selectively measure in real-time Glu fluxes released via exocytosis by large Glu vesicles (ca. 125 nm diameter) present in single hippocampal axonal varicosities as well as their intravesicular content before exocytosis. These measurements revealed a sub-quantal release mode in living hippocampal neurons, viz., only ca. one third to one half of intravesicular Glu molecules are released by individual vesicles during exocytotic events. Importantly, this fraction remained practically the same when hippocampal neurons were pretreated with L-Glu-precursor L-glutamine, while it significantly increased after zinc treatment, although in both cases the intravesicular contents were drastically affected.
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http://dx.doi.org/10.1002/anie.202100882DOI Listing
July 2021

All-yarn triboelectric nanogenerator and supercapacitor based self-charging power cloth for wearable applications.

Nanotechnology 2021 May 14;32(31). Epub 2021 May 14.

Functional Materials Laboratory, College of Materials Science and Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, People's Republic of China.

Despite rapid developments, multifunctional wearable electronics are still not significant in practical applications as compared to portable and stretchable power devices. In this paper, we present the flexible and easy large-scale production of single-electrode mode triboelectric nanogenerator (TENG) and supercapacitor yarn-based self-charging power fabric, for simultaneously converting and storing biomechanical energy. Fabricated using traditional knitting technologies, the self-charging power fabric can adapt to complex mechanical deformations owing to its high flexibility and stretchability. Additionally, the output characteristics of the TENG fabric were systematically investigated with the purpose of energy generation. The TENG fabric can generate a maximum peak power density of ∼90 mW·musing nylon as the contact material, with an operating frequency of 4 Hz. The as-prepared yarn-based supercapacitor exhibited high capacitance, good cycling stability, and flexibility, making it an appropriate wearable energy-storage device. Moreover, the proposed design uses energy harvested from biomechanical motions to sustainably power portable electronic devices. The results of this study indicate that the proposed design is a promising sustainable power source for wearable electronic devices.
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http://dx.doi.org/10.1088/1361-6528/abfcfeDOI Listing
May 2021

Pathway-Based Drug Repurposing with DPNetinfer: A Method to Predict Drug-Pathway Associations via Network-Based Approaches.

J Chem Inf Model 2021 05 26;61(5):2475-2485. Epub 2021 Apr 26.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Identification of drug-pathway associations plays an important role in pathway-based drug repurposing. However, it is time-consuming and costly to uncover new drug-pathway associations experimentally. The drug-induced transcriptomics data provide a global view of cellular pathways and tell how these pathways change under different treatments. These data enable computational approaches for large-scale prediction of drug-pathway associations. Here we introduced DPNetinfer, a novel computational method to predict potential drug-pathway associations based on substructure-drug-pathway networks via network-based approaches. The results demonstrated that DPNetinfer performed well in a pan-cancer network with an AUC (area under curve) = 0.9358. Meanwhile, DPNetinfer was shown to have a good capability of generalization on two external validation sets (AUC = 0.8519 and 0.7494, respectively). As a case study, DPNetinfer was used in pathway-based drug repurposing for cancer therapy. Unexpected anticancer activities of some nononcology drugs were then identified on the PI3K-Akt pathway. Considering tumor heterogeneity, seven primary site-based models were constructed by DPNetinfer in different drug-pathway networks. In a word, DPNetinfer provides a powerful tool for large-scale prediction of drug-pathway associations in pathway-based drug repurposing. A web tool for DPNetinfer is freely available at http://lmmd.ecust.edu.cn/netinfer/.
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http://dx.doi.org/10.1021/acs.jcim.1c00009DOI Listing
May 2021

Homotropic Cooperativity of Midazolam Metabolism by Cytochrome P450 3A4: Insight from Computational Studies.

J Chem Inf Model 2021 05 22;61(5):2418-2426. Epub 2021 Apr 22.

Department of Theoretical Chemistry and Biology, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), KTH Royal Institute of Technology, SE-106 91 Stockholm, Sweden.

Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of ∼50% clinically used drugs. Midazolam (MDZ) is a commonly used sedative drug and serves as a marker substrate for the CYP3A4 activity assessment. MDZ is metabolized by CYP3A4 to two hydroxylation products, 1'-OH-MDZ and 4-OH-MDZ. It has been reported that the ratio of 1'-OH-MDZ and 4-OH-MDZ is dependent on the MDZ concentration, which reflects the homotropic cooperative behavior in MDZ metabolism by CYP3A4. Here, we used quantum chemistry (QC), molecular docking, conventional molecular dynamics (cMD), and Gaussian accelerated molecular dynamics (GaMD) approaches to investigate the mechanism of the interactions between CYP3A4 and MDZ. QC calculations suggest that C1' is less reactive for hydroxylation than C4, which is a pro-chirality carbon. However, the 4-OH-MDZ product is likely to be racemic due to the chirality inversion in the rebound step. The MD simulation results indicate that MDZ at the peripheral allosteric site is not stable and the binding modes of the MDZ molecules at the productive site are in line with the experimental observations.
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http://dx.doi.org/10.1021/acs.jcim.1c00266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278384PMC
May 2021

Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury.

Hereditas 2021 Apr 16;158(1):13. Epub 2021 Apr 16.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277, Jiefang Avenue, Wuhan, 430022, China.

Background: Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI).

Methods: Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI.

Results: We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future.

Conclusions: Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.
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http://dx.doi.org/10.1186/s41065-021-00176-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052759PMC
April 2021

Letter by Chen et al Regarding Article, "gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration".

Circulation 2021 Apr 12;143(15):e811-e812. Epub 2021 Apr 12.

College of Chemistry & Chemical Engineering, Yangzhou University, China (Z.Y.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052195DOI Listing
April 2021

Precisely Controlled Vertical Alignment in Mesostructured Carbon Thin Films for Efficient Electrochemical Sensing.

ACS Nano 2021 Apr 6;15(4):7713-7721. Epub 2021 Apr 6.

Laboratory of Advanced Materials, Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Fudan University, Shanghai 200433, People's Republic of China.

Two-dimensional carbon materials, incorporating a large mesoporosity, are attracting considerable research interest in various fields such as catalysis, electrochemistry, and energy-related technologies owing to their integrated functionalities. However, their potential applications, which require favorable mass transport within mesopore channels, are constrained by the undesirable and finite mesostructural configurations due to the immense synthetic difficulties. Herein, we demonstrate an oriented monomicelle assembly strategy, for the facile fabrication of highly ordered mesoporous carbon thin films with vertically aligned and permeable mesopore channels. Such a facile and reproducible approach relies on the swelling and fusion effect of hydrophobic benzene homologues for directional monomicelle assembly. The orientation assembly process shows precise controllability and great universality, affording mesoporous carbon films with a cracking-free structure over a centimeter in size, highly tunable thicknesses (13 to 85 nm, an interval of ∼12 nm), mesopore size (8.4 to 13.5 nm), and switchable growth substrates. Owing to their large permeable mesopore channels, electrochemical sensors based on vertical mesoporous carbon films exhibit an ultralow limit of detection (50 nmol L) and great sensitivity in dopamine detection.
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http://dx.doi.org/10.1021/acsnano.1c01367DOI Listing
April 2021

Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia.

Bioorg Med Chem 2021 May 19;37:116109. Epub 2021 Mar 19.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China. Electronic address:

A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
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http://dx.doi.org/10.1016/j.bmc.2021.116109DOI Listing
May 2021

Ferroptosis-Related Long Non-Coding RNA signature predicts the prognosis of Head and neck squamous cell carcinoma.

Int J Biol Sci 2021 31;17(3):702-711. Epub 2021 Jan 31.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

: Head and neck squamous cell carcinoma (HNSCC) are head and neck cancers. On the other hand, ferroptosis is a novel iron-dependent and ROS reliant type of cell death observed various disease conditions. : We constructed a prognostic multilncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HNSCC. : We identified 25 differently expressed lncRNAs associated with prognosis of HNSCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HNSCC. Moreover, the AUC of the lncRNAs signature was 0.782, underscoring their utility in prediction HNSCC prognosis. Indeed, our risk assessment model was superior to traditional clinicopathological features in predicting HNSCC prognosis. GSEA revealed the immune and tumor-related pathways in the low risk group individuals. Moreover, TCGA revealed T cell functions including cytolytic activity, HLA, regulation of inflammationp, co-stimulation, co-inhibition and coordination of type II INF response were significantly different between the low-risk and high-risk groups. Immune checkpoints such as PDCD-1 (PD-1), CTLA4 and LAG3, were also expressed differently between the two risk groups. A novel ferroptosis-related lncRNAs signature impacts on the prognosis of HNSCC.
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http://dx.doi.org/10.7150/ijbs.55552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975700PMC
January 2021

Extracts from Chinese herbs with anti-amyloid and neuroprotective activities.

Int J Biol Macromol 2021 May 3;179:475-484. Epub 2021 Mar 3.

Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Košice, Slovakia. Electronic address:

Many Chinese herbs are well known for their neuroprotective and anti-oxidant properties. Extracts of Salvia miltiorrhiza and Anemarrhenae asphodeloides, tanshinone IIA (tanIIA), salvianolic acid B (Sal B) and sarsasapogenin (ML-1), were selected to study their dissociation potential towards Aβ peptide fibrils and neuroprotective effect on cells. Moreover, derivatives of sarsasapogenin (ML-2, ML-3 and ML-4) have been prepared by the addition of modified carbamate moiety. TanIIA and Sal B have shown to possess a strong ability to dissociate Aβ fibrils. The dissociation potential of ML-1 increased upon the introduction of carbamate moiety with N-heterocycles. In silico data revealed that derivatives ML-4 and Sal B interact with Aβ regions responsible for fibril stabilization through hydrogen bonds. Contrary, tanIIA binds close to a central hydrophobic region, which may lead to destabilization of fibrils. Sarsasapogenin derivative ML-2 decreased nitride oxide production, and derivative ML-4 enhanced the growth of neurites. The reported data highlight the possibility of using active compounds to design novel treatment agents for Alzheimer's disease.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.013DOI Listing
May 2021

Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer.

Sci Rep 2021 Mar 1;11(1):4841. Epub 2021 Mar 1.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan-Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research.
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http://dx.doi.org/10.1038/s41598-021-84403-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921437PMC
March 2021

Assessment of CYP2C9 Structural Models for Site of Metabolism Prediction.

ChemMedChem 2021 Jun 18;16(11):1754-1763. Epub 2021 Mar 18.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 20023, P. R. China.

Structure-based prediction of a compound's potential sites of metabolism (SOMs) mediated by cytochromes P450 (CYPs) is highly advantageous in the early stage of drug discovery. However, the accuracy of the SOMs prediction can be influenced by several factors. CYP2C9 is one of the major drug-metabolizing enzymes in humans and is responsible for the metabolism of ∼13 % of clinically used drugs. In this study, we systematically evaluated the effects of protein crystal structure models, scoring functions, heme forms, conserved active-site water molecules, and protein flexibility on SOMs prediction of CYP2C9 substrates. Our results demonstrated that, on average, ChemScore and GlideScore outperformed four other scoring functions: Vina, GoldScore, ChemPLP, and ASP. The performance of the crystal structure models with pentacoordinated heme was generally superior to that of the hexacoordinated iron-oxo heme (referred to as Compound I) models. Inclusion of the conserved active-site water molecule improved the prediction accuracy of GlideScore, but reduced the accuracy of ChemScore. In addition, the effect of the conserved water on SOMs prediction was found to be dependent on the receptor model and the substrate. We further found that one of snapshots from molecular dynamics simulations on the apo form can improve the prediction accuracy when compared to the crystal structural model.
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http://dx.doi.org/10.1002/cmdc.202000964DOI Listing
June 2021

The Relationship Between Otitis Media With Effusion and Gastroesophageal Reflux Disease: A Meta-analysis.

Otol Neurotol 2021 03;42(3):e245-e253

Department of Otolaryngology Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Objective: Recent studies have investigated the mechanism by which refluxed gastric materials reach the middle ear, to establish otitis media with effusion (OME) causal relation between them in both children and adults. Therefore, the relationship between OME and gastro-esophageal reflux disease (GERD) should be further studied extensively.

Methods: To identify eligible original articles, we searched a range of computerized databases, including Medline via PubMed, EMBASE, CNKI, and Web of Science with a systematic searching strategy. Subgroup analysis was performed to analyze heterogeneity and Egger and Begg funnel plot to assess the publication bias of the included articles.

Results: The meta-analysis had an overall sample size of 1961. We identified a significant relationship between OME and GERD, with a pooled odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.42-8.44; p < 0.001). The pooled data were calculated with the random-effects model as a high significant heterogeneity was found among the studies and there was no significant publication bias observed.

Conclusions: The meta-analysis suggested that there was a significant association between otitis media with effusion and gastroesophageal reflux disease.
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http://dx.doi.org/10.1097/MAO.0000000000002945DOI Listing
March 2021

DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients.

Cancer Control 2021 Jan-Dec;28:1073274820988519

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: Epigenetic changes are tightly linked to tumorigenesis development and malignant transformation' However, DNA methylation occurs earlier and is constant during tumorigenesis. It plays an important role in controlling gene expression in cancer cells.

Methods: In this study, we determining the prognostic value of molecular subtypes based on DNA methylation status in breast cancer samples obtained from The Cancer Genome Atlas database (TCGA).

Results: Seven clusters and 204 corresponding promoter genes were identified based on consensus clustering using 166 CpG sites that significantly influenced survival outcomes. The overall survival (OS) analysis showed a significant prognostic difference among the 7 groups (p<0.05). Finally, a prognostic model was used to estimate the results of patients on the testing set based on the classification findings of a training dataset DNA methylation subgroups.

Conclusions: The model was found to be important in the identification of novel biomarkers and could be of help to patients with different breast cancer subtypes when predicting prognosis, clinical diagnosis and management.
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http://dx.doi.org/10.1177/1073274820988519DOI Listing
January 2021

In silico prediction of mitochondrial toxicity of chemicals using machine learning methods.

J Appl Toxicol 2021 Jan 20. Epub 2021 Jan 20.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Mitochondria are important organelles in human cells, providing more than 95% of the energy. However, some drugs and environmental chemicals could induce mitochondrial dysfunction, which might cause complex diseases and even worsen the condition of patients with mitochondrial damage. Some drugs have been withdrawn from the market due to their severe mitochondrial toxicity, such as troglitazone. Therefore, there is an urgent need to develop models that could accurately predict the mitochondrial toxicity of chemicals. In this paper, suitable data were obtained from literature and databases first. Then nine types of fingerprints were used to characterize these compounds. Finally, different algorithms were used to build models. Meanwhile, the applicability domain of the prediction models was defined. We have also explored the structural alerts of mitochondrial toxicity, which would be helpful for medicinal chemists to better predict mitochondrial toxicity and further optimize lead compounds.
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http://dx.doi.org/10.1002/jat.4141DOI Listing
January 2021
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