Publications by authors named "Aijing Li"

19 Publications

  • Page 1 of 1

Exposure to legacy and novel perfluoroalkyl substance disturbs the metabolic homeostasis in pregnant women and fetuses: A metabolome-wide association study.

Environ Int 2021 May 13;156:106627. Epub 2021 May 13.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.

Background: Perfluoroalkyl substances (PFASs) exist extensively and several of these have been verified to be toxic. Prenatal exposure to PFASs has attracted much attention. Metabolome-wide association analyses can be used to explore the toxicity mechanisms of PFASs by identifying associated biomarkers.

Objectives: To evaluate associations between the metabolites in maternal and cord serum and internal exposure to several common PFASs.

Methods: Paired maternal and cord serum samples were collected from 84 pregnant women who gave birth between 2015 and 2016. Seven legacy and two novel PFASs were measured. A nontarget metabolomic method and an iterative metabolite annotation based on metabolic pathways were applied to characterize the metabolic profiles. Linear regression adjusted with the false discovery rate and covariates was used to indicate the associations.

Results: A total of 279 features in maternal serum and 338 features in cord serum were identified as metabolites associated with PFAS exposure. Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS) were two PFASs associated with more metabolites, while the two novel chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) showed less relevance to the metabolome. With pathway enrichment analysis, we found that three fatty acid metabolisms and retinol metabolism were correlated with PFAS exposure in maternal blood, and that sterol metabolism showed the correlation in both maternal serum and cord serum.

Conclusions: We identified metabolites and pathways in pregnant women and fetuses associated with the exposure to several PFAS, indicating a promising application for metabolome-wide association studies. Additional research is needed to confirm causation.
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http://dx.doi.org/10.1016/j.envint.2021.106627DOI Listing
May 2021

Tetrabromobisphenol A induces THR β-mediated inflammation and uterine injury in mice at environmentally relevant exposure concentrations.

J Hazard Mater 2021 04 15;407:124859. Epub 2020 Dec 15.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.

Tetrabromobisphenol A (TBBPA) is a widely used flame retardant, but the adverse outcomes induced by TBBPA has not been fully elucidated. In this study, TBBPA was detected in 54.9% of 102 female Chinese volunteers with an average serum concentration of 0.34 ng/mL. To investigate whether TBBPA induces adverse outcomes at environmentally relevant exposure doses, the mice were exposed to TBBPA for 14 and 28 days. The internal doses of TBBPA in mice serum were nearly the internal doses in volunteers. TBBPA significantly increased the secretion of some pro-inflammatory cytokines and suppressed immune responses in mice under such serum concentrations after 14- and 28-days exposure. Interestingly, uterine edema was observed in TBBPA-treated mice. In primary uterine cells model, the results showed TBBPA exposure suppressed THRβ expression, leading to the activation of the inflammatory PI3K/NF-κB signaling pathway. Our findings indicated that the uterus is the susceptible target organ of TBBPA and TBBPA exposure might increase risk of uterine cancer through deregulating inflammation pathways.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124859DOI Listing
April 2021

Tetrachlorobisphenol A induced immunosuppression and uterine injury in mice.

Ecotoxicol Environ Saf 2021 Jan 3;207:111527. Epub 2020 Nov 3.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Science, Beijing 100085, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Tetrachlorobisphenol A (TCBPA) is used as flame retardant, and it has been widely detected in the environmental and human samples. TCBPA is an endocrine disrupting chemical, but its effects on the immune system remains poorly understood. Here the effects of TCBPA on immune system were studied using combined in vivo and in vitro assays. Results showed that TCBPA could suppress the immune response in BALB/c mice via reducing the ratio of CD3 T lymphocytes to regulatory T cells. Moreover, TCBPA exposure significantly induced the increasing secretion of four pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) and four anti-inflammatory cytokines (IL-4, IL-5, IL-10, GM-CSF) in mice serum. Interestingly, uterine edema was observed in over 80% TCBPA-treated mice after 14- day exposure. TCBPA was detected in 18.6% serum samples of 150 female volunteers in this study. Therefore, our findings provided evidence that TCBPA exposure may cause adverse outcomes on immune system and uterus, suggesting that environmental exposure of TCBPA, as well as its adverse effects on human health should be of concern.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111527DOI Listing
January 2021

Tetrabromobisphenol A Perturbs Erythropoiesis and Impairs Blood Circulation in Zebrafish Embryos.

Environ Sci Technol 2020 10 8;54(20):12998-13007. Epub 2020 Sep 8.

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

Tetrabromobisphenol A (TBBPA), a ubiquitous environmental pollutant, has been implicated in developmental toxicity of aquatic animals. However, the impact of TBBPA on development and the related mechanism have not been fully elucidated. In this study, using a live imaging technique and transgenic labeling of zebrafish embryos, we described the toxic effects of TBBPA on hematopoietic development in zebrafish. We demonstrated that TBBPA induced erythroid precursor expansion in the intermediate cell mass (ICM), which perturbed the onset of blood circulation at 24-26 hours postfertilization (hpf). Consequently, excessive blood cells accumulated in the posterior blood island (PBI) and vascular cells formed defective caudal veins (CVs), preventing blood cell flow to the heart at 32-34 hpf. We found that the one-cell to 50% epiboly stage was the most sensitive period to TBBPA exposure during hematopoietic development. Furthermore, our results demonstrated that PBI malformation induced by TBBPA resulted from effects on erythroid precursor cells, which might involve THR signaling in complex ways. These findings will improve the understanding of TBBPA-induced developmental toxicity in teleost.
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http://dx.doi.org/10.1021/acs.est.0c02934DOI Listing
October 2020

Concentration and distribution of parabens, triclosan, and triclocarban in pregnant woman serum in China.

Sci Total Environ 2020 Mar 28;710:136390. Epub 2019 Dec 28.

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 100049, China.

Despite mass production and widespread use of parabens, triclosan (TCS), and triclocarban (TCC) in a range of personal care products, little is known about their concentrations and distribution in pregnant woman serum in China. In this study, 5 parabens (methyl- (MeP), ethyl- (EtP), butyl- (BuP), heptyl- (HeP) and benzyl-parabens (BzP)) and 4 their metabolites (methyl protocatechuate (OH-MeP), ethyl protocatechuate (OH-EtP), 3,4-dihydroxybenzoic acid (3,4-DHB) and 4-hydroxybenzoic acid (4-HB)), TCS, and TCC were measured, by using solid-phase extraction (SPE) and ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) techniques, in pregnant woman serum samples collected from 13 provinces in China. Total concentrations of parabens (∑PBs), their metabolites (∑MBs), and TCC and TCS (∑AAs) in serum ranged from 0.221-18.6 (geometric mean (GM): 2.47), 47.4-598 (212), and 0.101-5.84 (1.01) ng/mL, respectively. MeP, EtP, 4-HB and TCS were the dominant compounds, and their GM concentrations were 1.86, 0.239, 211 and 1.00 ng/mL, respectively. Geographical distribution of target chemicals in serum was determined. Concentrations of MeP (5.49 ng/mL) and EtP (0.895 ng/mL) in sera from the Northeast China were higher than those from other regions (MeP: 0.987-3.54, EtP: 0.07-0.254 ng/mL; p < 0.05). The highest 4-HB concentrations were found in sera from the Southwest China (GM: 286 ng/mL), whereas the TCS concentrations in sera from the North China (1.18 ng/mL) were higher than those found for other regions (p < 0.05). The estimated daily intakes (EDIs; range: 49.5-126 μg/kg body weight (bw)/day) showed that the Chinese women were in a low health risk from exposure to such chemicals. This is the first study to report concentration profiles of parabens, TCS and TCC in pregnant woman serum in China.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136390DOI Listing
March 2020

Serum concentration of bisphenol analogues in pregnant women in China.

Sci Total Environ 2020 Mar 12;707:136100. Epub 2019 Dec 12.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Science, Beijing 100085, PR China.

There is increasing concern regarding human exposure to bisphenol analogues (BPs) due to their widespread use and potentially adverse effects. Nevertheless, information on the occurrence of BPs in pregnant women is limited. In this study, BPs were detected in 181 serum samples from pregnant Chinese women. Ten BPs, including bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol P (BPP), bisphenol Z (BPZ), bisphenol AP (BPAP), tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), and tetrachlorobisphenol A (TCBPA), were positively identified and quantified in serum samples with total BP concentrations (sum of bisphenols: ∑BPs) of 0-144 ng/mL. Concentrations of the two frequently detected compounds, TBBPS and BPS, were 0.593 and 0.113 ng/mL, respectively. The results were also compared with the geographic distributions of the BPs. To our knowledge, this is the first time that TBBPS and TCBPA have been detected in serum samples of pregnant women. These findings suggest that additional studies are urgently needed to identify the risk of maternal and fetal exposure to these compounds.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136100DOI Listing
March 2020

Trajectory Planning for Data Collection of Energy-Constrained Heterogeneous UAVs.

Sensors (Basel) 2019 Nov 8;19(22). Epub 2019 Nov 8.

College of Communications Engineering, Army Engineering University of PLA, Nanjing 210042, China.

Nowadays, Unmanned Aerial Vehicles (UAVs) have received growing popularity in the Internet-of-Things (IoT) which often deploys many sensors in a relatively wide region. Since the battery capacity is limited, sensors cannot transmit over a long distance. It is necessary for designing efficient sensor data collection mechanisms to prolong the lifetime of the IoT and enhance data collection efficiency. In this paper, we consider a UAV-enabled data collection scenario, where multiple heterogeneous UAVs with different energy constraints are employed to collect data from sensors. The value of data depends on the importance of the monitoring area of the sensor and the freshness of collected data. Our objective is to maximize the data collection utility by jointly optimizing the communication scheduling and trajectory of each UAV. The data collection utility is determined by the amount and value of the collected data. This problem is a variant of multiple knapsack problem, which is a classical NP-hard problem. First, we transform the initial problem into a submodular function maximization problem under energy constraints, and then we design a novel trajectory planning algorithm to maximize the data collection utility, while accounting for different values of data and different energy constraints of heterogeneous UAVs. Finally, under different network settings, the performance of the proposed trajectory planning algorithm is evaluated via extensive simulations. The results show that the proposed algorithm can obtain maximum data collection utility.
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http://dx.doi.org/10.3390/s19224884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891348PMC
November 2019

A pilot study of mothers and infants reveals fetal sex differences in the placental transfer efficiency of heavy metals.

Ecotoxicol Environ Saf 2019 Dec 9;186:109755. Epub 2019 Oct 9.

Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.

It has been demonstrated that heavy metals cross the placental barrier and exert potentially harmful fetal effects. Although previous studies showed sex differences in response to similar intrauterine environments, little is known about fetal sex-related differences in placental transfer and accumulation of heavy metals. This study aimed to reveal the sex-specific risk of fetal exposure to heavy metals in pregnant women. We detected the exposure levels of eight heavy metals in 64 paired mother-infant maternal blood, cord blood and placental tissue samples. We found that the placental transfer efficiency (PTE) of titanium (Ti) and silver (Ag) was significantly higher in the group with male fetuses than that with female fetuses. The group with male fetuses had a larger placental:maternal blood ratio of Ag levels than the group with female fetuses, indicating fetal sex-related differences in placental transfer and accumulation of Ag. Prospective research should focus on the sex differences of adverse health effects induced by heavy metals and other pollutants.
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http://dx.doi.org/10.1016/j.ecoenv.2019.109755DOI Listing
December 2019

Completion Time Minimization for Multi-UAV Information Collection via Trajectory Planning.

Sensors (Basel) 2019 Sep 18;19(18). Epub 2019 Sep 18.

College of Communications Engineering, Army Engineering University of PLA, Nanjing 210042, China.

Unmanned Aerial Vehicles (UAVs) are widely used as mobile information collectors for sensors to prolong the network time in Wireless Sensor Networks (WSNs) due to their flexible deployment, high mobility, and low cost. This paper focuses on the scenario where rotary-wing UAVs complete information collection mission cooperatively. For the first time, we study the problem of minimizing the mission completion time for a multi-UAV system in a monitoring scenario when considering the information collection quality. The mission completion time includes flying time and hovering time. By optimizing the trajectories of all UAVs, we minimize the mission completion time while ensuring that the information of each sensor is collected. This problem can be formulated as a mixed-integer non-convex one which has been proved to be NP-hard. To solve the formulated problem, we first propose a hovering point selection algorithm to select appropriate hovering points where the UAVs can sequentially collect the information from multiple sensors. We model this problem as a BS coverage problem with the information collection quality in consideration. Then, we use a min-max cycle cover algorithm to assign these hovering points and get the trajectory of each UAV. Finally, with the obtained UAVs trajectories, we further consider the UAVs can also collect information when flying and optimize the time allocations. The performance of our algorithm is verified by simulations, which show that the mission completion time is minimum compared with state-of-the-art algorithms.
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http://dx.doi.org/10.3390/s19184032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767661PMC
September 2019

Structural Basis and Mechanism for Vindoline Dimers Interacting with α,β-Tubulin.

ACS Omega 2019 Jul 10;4(7):11938-11948. Epub 2019 Jul 10.

College of Chemical Science and Technology and Pharmacy, Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, Yunnan University, Kunming 650091, China.

Vinblastine and its derivatives used in clinics as antitumor drugs often cause drug resistance and some serious side effects; thus, it is necessary to study new vinblastine analogues with strong anticancer cytotoxicity and low toxicity. We designed a dimer molecule using two vindoline-bonded dimer vindoline (DVB) and studied its interaction with α,β-tubulin through the double-sided adhesive mechanism to explore its anticancer cytotoxicity. In our work, DVB was docked into the interface between α-tubulin and β-tubulin to construct a complex protein structure, and then it was simulated for 100 ns using the molecular dynamics technology to become a stable and refined complex protein structure. Based on such a refined structure, the quantum chemistry at the level of the MP2/6-31G(d,p) method was used to calculate the binding energies for DVB interacting with respective residues. By the obtained binding energies, the active site residues for interaction with DVB were found. Up to 20 active sites of residues within α,β-tubulin interacting with DVB are labeled in β-Asp179, β-Glu207, β-Tyr210, β-Asp211, β-Phe214, β-Pro222, β-Tyr224, and β-Leu227 and α-Asn249, α-Arg308, α-Lys326, α-Asn329, α-Ala333, α-Thr334, α-Lys336, α-Lys338, α-Arg339, α-Ser340, α-Thr349, and α-Phe351. The total binding energy between DVB and α,β-tubulin is about -251.0 kJ·mol. The sampling average force potential (PMF) method was further used to study the dissociation free energy (Δ) along the separation trajectory of α,β-tubulin under the presence of DVB based on the refined structure of DVB with α,β-tubulin. Because of the presence of DVB within the interface between α- and β-tubulin, Δ is 252.3 kJ·mol. In contrast to the absence of DVB, the separation of pure β-tubulin needs a free energy of 196.9 kJ·mol. The data show that the presence of DVB adds more 55.4 kJ·mol of Δ to hinder the normal separation of α,β-tubulin. Compared to vinblastine existing, the free energy required for the separation of α,β-tubulin is 220.5 kJ·mol. Vinblastine and DVB can both be considered through the same double-sided adhesive mechanism to give anticancer cytotoxicity. Because of the presence of DVB, a larger free energy is needed for the separation of α,β-tubulin, which suggests that DVB should have stronger anticancer cytotoxicity than vinblastine and shows that DVB has a broad application prospect.
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http://dx.doi.org/10.1021/acsomega.9b00947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682054PMC
July 2019

Diagnosis of coronary artery disease in patients with atrial fibrillation using low tube voltage coronary CT angiography with isotonic low-concentration contrast agent.

Int J Cardiovasc Imaging 2019 Dec 30;35(12):2239-2248. Epub 2019 Jul 30.

Diabetes Research Center, School of Medicine, Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, Zhejiang Province, People's Republic of China.

This prospective study evaluated the image quality and accuracy of coronary computed tomography angiography (CCTA) for diagnosing coronary artery disease (CAD) in patients with atrial fibrillation (AF), in which CCTA used adaptive iterative dose reduction (AIDR) with a low tube voltage and low concentration of isotonic contrast agent. Sixty-eight consecutive patients with AF and suspected CAD were equally and randomly apportioned to two groups and underwent CCTA. In the experimental group, the contrast agent was iodixanol (270 mg I/mL), patients were scanned with 100 kV, and reconstruction was by AIDR. In the conventional scanning (control) group, the contrast agent was iopromide (370 mg I/mL), patients were scanned with 120 kV, and reconstruction was by filtered back projection. The image quality, effective radiation dose (E), and total iodine intake of the groups were compared. Thirty-nine patients with coronary artery stenosis later were given invasive coronary angiography (ICA). The groups were similar with regard to mean CT value, noise, and signal-to-noise and contrast-to-noise ratios. The figure of merit of the experimental group was significantly higher than that of the control group, while the E and total iodine were significantly lower. Using ICA as the diagnostic reference, the groups shared similar sensitivity, specificity, and false positive and false negative rates for diagnosing coronary artery stenosis. For determining CAD in patients with AF, CCTA with isotonic low-concentration contrast agent and low-voltage scanning is a feasible alternative that improves accuracy and reduces radiation dose and iodine intake.
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http://dx.doi.org/10.1007/s10554-019-01678-7DOI Listing
December 2019

IILS: Intelligent imaging layout system for automatic imaging report standardization and intra-interdisciplinary clinical workflow optimization.

EBioMedicine 2019 Jun 23;44:162-181. Epub 2019 May 23.

Department of Radiology, the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.

Background: To achieve imaging report standardization and improve the quality and efficiency of the intra-interdisciplinary clinical workflow, we proposed an intelligent imaging layout system (IILS) for a clinical decision support system-based ubiquitous healthcare service, which is a lung nodule management system using medical images.

Methods: We created a lung IILS based on deep learning for imaging report standardization and workflow optimization for the identification of nodules. Our IILS utilized a deep learning plus adaptive auto layout tool, which trained and tested a neural network with imaging data from all the main CT manufacturers from 11,205 patients. Model performance was evaluated by the receiver operating characteristic curve (ROC) and calculating the corresponding area under the curve (AUC). The clinical application value for our IILS was assessed by a comprehensive comparison of multiple aspects.

Findings: Our IILS is clinically applicable due to the consistency with nodules detected by IILS, with its highest consistency of 0·94 and an AUC of 90·6% for malignant pulmonary nodules versus benign nodules with a sensitivity of 76·5% and specificity of 89·1%. Applying this IILS to a dataset of chest CT images, we demonstrate performance comparable to that of human experts in providing a better layout and aiding in diagnosis in 100% valid images and nodule display. The IILS was superior to the traditional manual system in performance, such as reducing the number of clicks from 14·45 ± 0·38 to 2, time consumed from 16·87 ± 0·38 s to 6·92 ± 0·10 s, number of invalid images from 7·06 ± 0·24 to 0, and missing lung nodules from 46·8% to 0%.

Interpretation: This IILS might achieve imaging report standardization, and improve the clinical workflow therefore opening a new window for clinical application of artificial intelligence. FUND: The National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/j.ebiom.2019.05.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604879PMC
June 2019

Heavy metals in maternal and cord blood in Beijing and their efficiency of placental transfer.

J Environ Sci (China) 2019 Jun 14;80:99-106. Epub 2018 Nov 14.

Institute of Environment and Health, Jianghan University, Wuhan 430056, China; Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

This study aimed to determine the effect of exposure to heavy metals in pregnant women in Beijing, China. We also evaluated the association of these heavy metals with birth weight and length of newborns. We measured the levels of 10 heavy metals, including lead (Pb), titanium (Ti), manganese (Mn), nickel (Ni), cadmium (Cd), chromium (Cr), antimony (Sb), stannum (Sn), vanadium (V), and arsenic (As), in 156 maternal and cord blood pairs. An inductively coupled plasma mass spectrometry method was used for measurement. Pb, As, Ti, Mn, and Sb showed high detection rates (>50%) in both maternal and cord blood. Fourteen (9%) mothers had blood Pb levels greater than the United States Center for Disease Control allowable threshold limit for children (50 μg/L). In prenatal exposure to these heavy metals, there was no significant association between any heavy metal and birth weight/length. Moreover, we estimated the placental transfer efficiency of each heavy metal, and the median placental transfer efficiency ranged from 49.6% (Ni) to 194% (Mn) (except for Cd and Sn). The level and detection rate of Cd in maternal blood were much higher than that in cord blood, which suggested that Cd had difficulty in passing the placental barrier. Prospective research should focus on the source and risk of heavy metals in non-occupationally exposed pregnant women in Beijing.
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http://dx.doi.org/10.1016/j.jes.2018.11.004DOI Listing
June 2019

Double-sides sticking mechanism of vinblastine interacting with α,β-tubulin to get activity against cancer cells.

J Biomol Struct Dyn 2019 09 18;37(15):4080-4091. Epub 2018 Nov 18.

a 1 College of Chemical Science and Technology and Pharmacy, Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, Yunnan University , Kunming , P. R. China.

Vinblastine (VLB) and its derivatives have been used for clinical first-line drugs to treat various cancers. Due to the resistance and serious side effects from using VLB and its derivatives, there is a need to discover and develop novel VLB derivatives with high activity against cancer cells. In order to better discover and develop new VLB derivatives, we need to study the structural basis of VLB's anti-cancer cytotoxicity and the mechanism of its interaction with α,β-tubulins. Based on the crystal structure of α,β-microtubule complex protein, the molecular dynamics method including the sampling PMF method was used to study the variation of dissociation free energy (Δ) of α,β-tubulins under different system conditions, and then from which to study the mechanism of the interaction between VLB and α,β-tubulins. The obtained results show that the dissociation of pure α,β-tubulins requires 197.8 kJ·mol for Δ. When the VLB molecule exists between the interface of α,β-tubulins, the dissociation Δ of α,β-tubulins reaches 220.5 kJ·mol, which is greater than that of pure α,β-tubulin. The VLB molecule is formed by connecting a vindoline moiety (VM) molecule with a catharanthine moiety (CM) molecule through a carbon-carbon bond, which is a larger molecule. When the CM molecule exists in the middle of α,β-tubulin interface, the dissociation Δ of α,β-tubulins is 46.2 kJ·mol, during which the CM moves with β-tubulin. When the VM molecule exists between the middle of α,β-tubulin interface, the dissociation Δ of α,β-tubulins is 86.7 kJ·mol, during which it moves with α-tubulin. Therefore, the VLB molecule is like a double-sides tape to stick α-tubulin and β-tubulin together. The VLB molecule intervenes the dynamic equilibrium between dissociation and aggregation of α-tubulin and β-tubulin by a double-sides sticking mechanism to exert high activity with toxicity against cancer cell. Besides, our results demonstrate that VLB has its structural basis for anticancer cytotoxicity due to its two compositions composed of a CM molecule and a VM molecule although they have little toxicity against cancer cell alone.
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http://dx.doi.org/10.1080/07391102.2018.1539412DOI Listing
September 2019

[Association of parameters in dynamic contrast-enhanced MRI using reference region model with prognostic factors and molecular subtypes of breast cancer].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2017 May;46(5):505-510

Department of Radiology, Ningbo Second Hospital, Ningbo 315010, Zhejiang Province, China.

Objective: To investigate the association of parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using reference region model with prognostic factors and molecular subtypes of breast cancer.

Methods: MRI and pathological data of 50 patients with pathologically confirmed invasive ductal carcinoma of the breast were retrospectively analyzed. Reference region model was applied to analyze pharmacokinetic quantitative parameters including volume transfer constant (RR K), rate constant (K) and the ratio of K to extracellular space volume (K/V). The associations of the above parameters with prognostic factors and molecular subtypes of breast cancer were analyzed.

Results: RR K and K were significantly higher in patients of histological grade 3 compared with those of histological grade 1 & 2 (all <0.05); and the patients with estrogen receptor (ER)-negative and/or progesterone receptor (PR)-negative also had higher RR K and K than those with ER-positive or PR-positive (all <0.05). For immunohistochemistry, RR K and K were significantly higher in triple negative breast cancer compared with luminal type breast cancer (all <0.05).

Conclusions: High RR K and K are associated with poor prognosis of breast cancer, and which can also be used to distinguish molecular subtypes of breast cancer.
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May 2017

The feasibility of low-concentration contrast and low tube voltage in computed tomography perfusion imaging: an animal study.

Biosci Rep 2018 02 10;38(1). Epub 2018 Jan 10.

Department of Radiology, Ningbo No.2 Hospital, Ningbo, China

Aim To investigate the feasibility of low-concentration contrast (270 mg/ml) together with low tube voltage (80 kV) and adaptive iterative dose reduction (AIDR)-3D reconstruction in liver computed tomography (CT) perfusion imaging.Method A total of 15 healthy New Zealand rabbits received two CT scans each. The first scan (control) was acquired at 100 kV and 100 mA with iopromide (370 mg/ml), while the second scan (experimental) was acquired at 80 kV and 100 mA with iodixanol (270 mg/ml) 24 h after the first scan. The obtained images were reconstructed with filtered back projection (FBP) and AIDR-3D in the control and experimental groups respectively. The perfusion parameters (hepatic artery perfusion [HAP], portal vein perfusion [PVP], hepatic perfusion index [HPI], and total liver perfusion [TLP]) and image quality (image quality score, average CT value of abdomen aorta, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and figure of merit [FOM]) were compared using a paired -test or Mann-Whitney test between the two groups, when appropriate. The effective radiation dose and iodine intake were also recorded and compared.Results With the exception of the FOM criteria, the image quality and perfusion parameters were not significantly different between the two groups. The effective radiation dose and iodine intake were 38.79% and 27.03% lower respectively, in the experimental group.Conclusion Low-concentration contrast (iodixanol, 270 mg/ml) together with low tube voltage (80 kV) and AIDR-3D reconstruction help to reduce radiation dose and iodine intake without compromising perfusion parameters and image quality in liver CT perfusion imaging.
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http://dx.doi.org/10.1042/BSR20170977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435459PMC
February 2018

Recent Advances in Superparamagnetic Iron Oxide Based Nanoprobes as Multifunctional Theranostic Agents for Breast Cancer Imaging and Therapy.

Curr Med Chem 2018 ;25(25):3001-3016

Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China.

Background: Breast cancer accounts for nearly one in three cancers, and it is the most common cancer diagnosed among women. The death rate of breast cancer is estimated to be 14%. Hence, accurate diagnosis in early stage and effective treatment in any stage are critical for the survival of breast cancer. Mammogram has been the most common technique administered to detect breast cancer. However, the radiation dose from mammogram is harmful to patients. Fortunately, magnetic resonance imaging (MRI) can diagnose breast cancer without any radiation dose, and enhanced MRI can make earlier and differential diagnosis. Therefore, as contrast materials, superparamagnetic iron oxide based nanoprobes (SPIONs) have generated a great deal of attention.

Objective: This review covers recent advances in SPIONs as multifunctional theranostic agents.

Methods: Besides synthesis and surface modification of SPIONs, passive and active targeted imaging is also discussed. Moreover, a serial of potential therapy for breast cancer is further described, such as photodynamic therapy, photothermal therapy, chemotherapy and magnetic hyperthermia therapy.

Conclusion: Preparation and surface modification of SPIONs is critical for imaging diagnosis of breast cancer and further potential treatment.
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http://dx.doi.org/10.2174/0929867324666170705144642DOI Listing
September 2018

Structural Basis and Mechanism of Chiral Benzedrine Molecules Interacting With Third Dopamine Receptor.

Chirality 2016 10 1;28(10):674-85. Epub 2016 Sep 1.

Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming, China.

In order to investigate the chiral benzedrine molecules corresponding to their different characteristics in biochemical systems, we studied their interaction with D3 R using the docking method, molecular dynamic simulation, and quantum chemistry. The obtained results indicate that the active residues for R-benzedrine (RAT) bound with D3 R are Ala132, Asp133, and Tyr55, while Asn57, Asp133, Asp168, Cys172, Gly54, Trp24, and Vall136 act as the active residues for S-benzedrine (SAT). The different active pockets are observed for ART or SAT because they possess different active residues. The binding energies between RAT and SAT with D3 R were determined to be -44.0 kJ.mol(-1) and -71.2 kJ.mol(-1) , respectively. These results demonstrate that SAT within the studied pocket of D3 R has a stronger capability of binding with D3 R, while it is more feasible for RAT to leave from the interior positions of D3 R. In addition, the results suggest that the D3 R protein can recognize chiral benzedrine molecules and influence their different addictive and pharmacological effects in biochemical systems. Chirality 28:674-685, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/chir.22630DOI Listing
October 2016

Molecular dynamics simulation of d-Benzedrine transmitting through molecular channels within DR.

J Biomol Struct Dyn 2017 Jun 5;35(8):1672-1684. Epub 2016 Aug 5.

a Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology and Pharmacy Academy , Yunnan University , Kunming 650091 , China.

Dex-Benzedrine (known as d-Benzedrine or SAT) acts in dopamine receptors of central nerve cell system. In clinic, SAT is used to treat a variety of diseases; meanwhile, it has dependence and addiction. In order to investigate the pharmacology and addiction mechanisms of SAT as a medicine, in this paper, we have studied the structure of DR complex protein with SAT, and based on which, using potential mean force with umbrella samplings and the simulated phospholipid bilayer membrane (or POPC bilayer membrane), the molecular dynamics simulation was performed to obtain free energy changes upon the trajectories for SAT moving along the molecular channels within DR. The free energy change for SAT transmitting toward the outside of cell along the functional molecular channel within DR is 83.5 kJ mol. The change of free energy for SAT to permeate into the POPC bilayer membrane along the protective molecular channel within DR is 87.7 kJ mol. Our previous work gave that the free energy for Levo-Benzedrine (RAT) transmitting toward the outside of cell along the functional molecular channel within DR is 91.4 kJ mol, while it is 117.7 kJ mol for RAT to permeate into the POPC bilayer membrane along the protective molecular channel within DR. The values of free energy suggest that SAT relatively prefers likely to pass through the functional molecular channel within DR for increasing the release of dopamine molecules resulting in a variety of functional effects for SAT. The obtained results show that the pharmacology and addiction mechanisms of SAT as a drug are closely related to the molecular dynamics and mechanism for SAT transmitting along molecular channels within DR.
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http://dx.doi.org/10.1080/07391102.2016.1190947DOI Listing
June 2017