Publications by authors named "Yifan Luo"

34 Publications

Biomimetic Dendrimer-Peptide Conjugates for Early Multi-Target Therapy of Alzheimer's Disease by Inflammatory Microenvironment Modulation.

Adv Mater 2021 May 17:e2100746. Epub 2021 May 17.

Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Pharmaceutics School of Pharmacy, Fudan University, Shanghai, 201203, P. R. China.

Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on β-amyloid (Aβ) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD. Based on the crosstalk between inflammatory response and brain cells, a reactive oxygen species (ROS)-responsive dendrimer-peptide conjugate (APBP) is devised to target the AD microenvironment and inhibit inflammatory responses at an early stage. With the modification of the targeting peptide, this nanoconjugate can efficiently deliver peptides to the infected regions and restore the antioxidant ability of neurons by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway. Moreover, this multi-target strategy exhibits a synergistic function of ROS scavenging, promoting Aβ phagocytosis, and normalizing the glial cell phenotype. As a result, the nanoconjugate can reduce ROS level, decrease Aβ burden, alleviate glial cell activation, and eventually enhance cognitive functions in APPswe/PSEN1dE9 model mice. These results indicate that APBP can be a promising candidate for the multi-target treatment of AD.
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http://dx.doi.org/10.1002/adma.202100746DOI Listing
May 2021

IP-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion.

Nat Commun 2021 04 28;12(1):2461. Epub 2021 Apr 28.

School of Life Sciences, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

COP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1-CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2 mice with partially disrupted binding of IP, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP-assisted CSN-COP1 competition. Deregulation of the IP-CSN-CRL4-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.
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http://dx.doi.org/10.1038/s41467-021-22941-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080631PMC
April 2021

Metal-Organic Framework-Derived Hierarchical MnO/Co with Oxygen Vacancies toward Elevated-Temperature Li-Ion Battery.

ACS Nano 2021 Mar 19;15(3):4594-4607. Epub 2021 Feb 19.

Guangzhou Key Laboratory of Materials for Energy Conversion and Storage, Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education, School of Chemistry, South China Normal University, Guangzhou 510006, China.

Transition metal oxides for high-temperature lithium-ion batteries have captivated orchestrated efforts for next-generation high-energy-density anodes. However, due to inherent low tap density, poor conductivity, and structural instability, their poor cyclability capacity and rate performance at elevated temperatures hinder further implementation. Oxygen vacancies (O) engineered by manipulating the active sites and electrical conductivity is a promising method for superior lithium storage. Herein, hierarchical MnO/Co nanoparticle-embedded -doped carbon nanotube (CNT)-assembled carbonaceous micropolyhedrons (O-MnO/Co NCPs) are constructed by a "4S" self-assembly, self-template, self-adaptive, and self-catalytic metal-organic framework template method with oxygen vacancies introduced. Impressively, the internal nanoparticles with metallic Co and the external -doped carbonaceous matrix entangled by fluffy self-generated CNTs synchronously constructed hierarchical micro/nano-secondary hybrids, facilitating highly compacted density, staggered conductive network, multidirectional diffusion pathways, and accelerated electrochemical kinetics. Experimental and density functional theory investigations systematically manifested that the O alongside the local built-in electric field within the crystal lattice induced the boosted electrical conductivity, additional active sites, and alleviated structural expansion, further achieving the exceptional diffusivity coefficient and pseudocapacitive capacity. Benefiting from the integrated structural and compositional optimization, the O-MnO/Co NCPs achieved distinguished "3C" performance with superior ultralong cyclability (a volumetric capacity of 1713.5 mAh cm at 1 A g up to 1000 cycles), good rate capacity (a well-maintained capacity of 670.2 mAh g even at 10 A g), and considerable high-temperature capability at 60 °C.
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http://dx.doi.org/10.1021/acsnano.0c08808DOI Listing
March 2021

Colon cancer-associated transcript-1 enhances glucose metabolism and colon cancer cell activity in a high-glucose environment and .

J Gastrointest Oncol 2020 Dec;11(6):1164-1185

Department of Pathology, School of Medicine and Nursing Sciences, Huzhou University, Huzhou Central Hospital, Huzhou, China.

Background: Our study aims to investigate the effect of colon cancer-associated transcript-1 (CCAT-1) on colon cancer cells' activity and metabolism under different glucose environments and .

Methods: The levels of proliferation, migration, glucose, lactic acid, glucose metabolism-related enzymes, apoptosis genes, epithelial-mesenchymal transition (EMT) marker proteins, and PI3K/Akt/C-MYC pathway in -silenced SW620 cells cultured with different glucose levels were tested. Twenty BALB/C nude mice with hyperglycemia or normal blood sugar were transplanted with -silenced SW620 cells, blood glucose levels, lactic acid, insulin, and volume of transplanted tumor cells, the expression of EMT marker proteins, and PI3K/Akt/C-MYC pathway was detected.

Results: The levels of proliferation, migration, glucose, lactic acid, LDH-A, PKM2, and HK2 decreased, apoptosis increased in SW620 cells cultured with low glucose or silenced (P<0.05); levels of E-cadherin and ZO-1 significantly increased, and levels of N-cadherin, vimentin, and p-Akt decreased in CCAT-1-silenced SW620 cells cultured with high glucose (P<0.05). Hyperglycemic nude mice transplanted with CCAT-1-silenced colon cancer cells showed decreased tumor volume, blood glucose, lactic acid, insulin, P-AKT, and P-C-MYC than EV group (P<0.05).

Conclusions: can enhance glucose metabolism and proliferation and migration of colon cancer cells by upregulating the expression of glycolysis enzymes, inhibiting apoptosis, activating the Akt/C-MYC pathway, and promoting EMT expression.
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http://dx.doi.org/10.21037/jgo-20-474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807285PMC
December 2020

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy.

J Am Soc Nephrol 2021 01 7;32(1):99-114. Epub 2020 Dec 7.

Regeneron Pharmaceuticals, Tarrytown, New York

Background: C3 glomerulopathy (C3G) is characterized by the alternative-pathway (AP) hyperactivation induced by nephritic factors or complement gene mutations. Mice deficient in complement factor H (CFH) are a classic C3G model, with kidney disease that requires several months to progress to renal failure. Novel C3G models can further contribute to understanding the mechanism behind this disease and developing therapeutic approaches.

Methods: A novel, rapidly progressing, severe, murine model of C3G was developed by replacing the mouse gene with the human homolog using VelociGene technology. Functional, histologic, molecular, and pharmacologic assays characterize the presentation of renal disease and enable useful pharmacologic interventions in the humanized C3 (C3) mice.

Results: The C3 mice exhibit increased morbidity early in life and die by about 5-6 months of age. The C3 mice display elevated biomarkers of kidney dysfunction, glomerulosclerosis, C3/C5b-9 deposition, and reduced circulating C3 compared with wild-type mice. Administration of a C5-blocking mAb improved survival rate and offered functional and histopathologic benefits. Blockade of AP activation by anti-C3b or CFB mAbs also extended survival and preserved kidney function.

Conclusions: The C3 mice are a useful model for C3G because they share many pathologic features consistent with the human disease. The C3G phenotype in C3 mice may originate from a dysregulated interaction of human C3 protein with multiple mouse complement proteins, leading to unregulated C3 activation AP. The accelerated disease course in C3 mice may further enable preclinical studies to assess and validate new therapeutics for C3G.
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http://dx.doi.org/10.1681/ASN.2020050698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894673PMC
January 2021

Lactoferrin for the treatment of COVID-19 (Review).

Exp Ther Med 2020 Dec 27;20(6):272. Epub 2020 Oct 27.

Department of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.

The coronavirus disease 2019 (COVID-19) outbreak was caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical outcomes of elderly individuals and those with underlying diseases affected by COVID-19 are serious, and may result in acute respiratory distress syndrome (ARDS) and even mortality. Currently, the clinical treatments for COVID-19 mostly involve symptom alleviation measures and non-specific broad spectrum antiviral drugs, as highly effective antiviral drugs and vaccines are not yet available. Lactoferrin (LF) is a safe iron-binding glycoprotein that is present in the milk of the majority of mammals and exhibits broad-spectrum antiviral activity, including against coronaviruses. In addition, LF also exhibits anti-inflammatory, anti-infective and immune-regulating properties, which are in line with the treatment requirements for SARS-CoV-2 infection. Therefore, the use of LF may be of value in the prevention and/or management of COVID-19. The aim of the present review was to summarize the previous reports on the antiviral properties of LF and compare these with the characteristics of SARS-CoV-2 infection, in order to determine whether LF could be used to assist in the prevention of COVID-19 and to investigate the possible underlying mechanisms governing its mode of action.
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http://dx.doi.org/10.3892/etm.2020.9402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664603PMC
December 2020

The Growth Trend Predictions in Pulmonary Ground Glass Nodules Based on Radiomic CT Features.

Front Oncol 2020 20;10:580809. Epub 2020 Oct 20.

Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China.

The management of ground glass nodules (GGNs) remains a distinctive challenge. This study is aimed at comparing the predictive growth trends of radiomic features against current clinical features for the evaluation of GGNs. A total of 110 GGNs in 85 patients were included in this retrospective study, in which follow up occurred over a span ≥2 years. A total of 396 radiomic features were manually segmented by radiologists and quantitatively analyzed using an Analysis Kit software. After feature selection, three models were developed to predict the growth of GGNs. The performance of all three models was evaluated by a receiver operating characteristic (ROC) curve. The best performing model was also assessed by calibration and clinical utility. After using a stepwise multivariate logistic regression analysis and dimensionality reduction, the diameter and five specific radiomic features were included in the clinical model and the radiomic model. The rad-score [odds ratio (OR) = 5.130; < 0.01] and diameter (OR = 1.087; < 0.05) were both considered as predictive indicators for the growth of GGNs. Meanwhile, the area under the ROC curve of the combined model reached 0.801. The high degree of fitting and favorable clinical utility was detected using the calibration curve with the Hosmer-Lemeshow test and the decision curve analysis was utilized for the nomogram. A combined model using the current clinical features alongside the radiomic features can serve as a powerful tool to assist clinicians in guiding the management of GGNs.
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http://dx.doi.org/10.3389/fonc.2020.580809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606974PMC
October 2020

Application of vancomycin in patients with augmented renal clearance.

Eur J Hosp Pharm 2020 09 9;27(5):276-279. Epub 2019 Jan 9.

Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.

Objective: To analyse the influence of factors on the steady-state trough concentration (C) of vancomycin, especially in patients with augmented renal clearance, and to provide a reference for clinical application.

Methods: Data on patient demographics, routine blood examination, hepatic function and kidney function were collected from May 2013 to October 2016. A total of 292 patients were enrolled and correlations between Cof vancomycin and other test indices were analysed by SPSS software.

Results: The patients with augmented renal clearance were significantly younger with relatively lower C values and higher weight, ALB and PLT compared to others. And age was the most important factor of Camong subgroups of ARC.

Conclusions: Inpatients with augmented renal clearance,vancomycin C was mainly affected by age. Clinicians and pharmacists should adjust the dosage regimen in a timely manner based on therapeutic drug monitoring and these influencing factors.
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http://dx.doi.org/10.1136/ejhpharm-2018-001781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447238PMC
September 2020

Understanding ring-closing and racemization to prepare α-amino acid NCA and NTA monomers: a DFT study.

Phys Chem Chem Phys 2020 Jul;22(26):14868-14874

Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China. and Department of Radiology, Jiulongpo People's Hospital, Chongqing 400050, China and Innovation Center for Minimally Invasive Techniques and Devices, Zhejiang University, Hangzhou 310016, China.

Polypeptides and polypeptoids are promising materials in biomedical applications bearing α-amino acid repeating units, which are prepared from ring-opening polymerizations of α-amino acid N-carboxyanhydride (NCA) or N-thiocarboxyanydride (NTA) monomers. Detailed studies on monomer synthetic routes are essential to explore new α-amino acid NCA and NTA monomers as well as the corresponding poly(α-amino acid) materials. In this contribution, density functional theory (DFT) is applied to investigate the mechanism of the Leuchs approach including two possible pathways, precursor structure and racemization in the ring-closing reaction. According to DFT calculations, pathway 2 is preferred with lower ΔG than pathway 1, and the rate-determining step is recognized as an SN2 substitution with releasing equivalent halogenated hydrocarbon, which explains our experimental observations. Racemization results from the reaction between the NTA monomer and a strong protonic acid, which can be suppressed by low temperature and short reaction time. Racemization is inhibited by steric hindrance in those NTAs of α-amino acids containing high bulkiness at the β-carbon, such as leucine-NTA.
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http://dx.doi.org/10.1039/d0cp01174fDOI Listing
July 2020

Molecular Magnetic Resonance Imaging with Contrast Agents for Assessment of Inflammatory Bowel Disease: A Systematic Review.

Contrast Media Mol Imaging 2020 6;2020:4764985. Epub 2020 May 6.

The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China.

Background And Aims: Magnetic resonance imaging (MRI) has taken an important role in the diagnosis of inflammatory bowel diseases (IBD). In the wake of current advances in nanotechnology, the drug delivery industry has seen a surge of nanoparticles advertising high specificity in target imaging. Given the rapid development of the field, this review has assembled related articles to explore whether molecular contrast agents can improve the diagnostic capability on gastrointestinal imaging, especially for IBD.

Methods: Relevant articles published between 1998 and 2018 from a literature search of PubMed and EMBASE were reviewed. Data extraction was performed on the studies' characteristics, experimental animals, modelling methods, nanoparticles type, magnetic resonance methods, and means of quantitative analysis.

Results: A total of 8 studies were identified wherein the subjects were animals, and all studies employed MR equipment. One group utilized a perfluorocarbon solution and the other 7 groups used either magnetic nanoparticles or gadolinium- (Gd-) related nanoparticles for molecular contrast. With ultrasmall superparamagnetic iron oxide (USPIO) particles and Gd-related nanoparticles, signal enhancements were found in the mucosa or with focal lesion of IBD-related model in T1-weighted images (T1WI), whereas superparamagnetic iron oxide (SPIO) particles showed a signal decrease in the intestinal wall of the model in T1WI or T2-weighted images. The signal-to-noise ratio (SNR) was employed to analyze bowel intensity in 3 studies. And the percentage of normalized enhancement was used in 1 study for assessing the severity of inflammation.

Conclusion: Molecular MRI with contrast agents can improve the early diagnosis of IBD and quantitate the severity of inflammation in experimental studies.
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http://dx.doi.org/10.1155/2020/4764985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225866PMC
May 2020

Synthesis and acetone sensing properties of ZnFeO/rGO gas sensors.

Beilstein J Nanotechnol 2019 16;10:2516-2526. Epub 2019 Dec 16.

College of Mechanical Engineering, Yangzhou University, Yangzhou 225127, P.R. China.

Hollow spheres of pure ZnFeO and of composites of ZnFeO and reduced graphene oxide (rGO) with different rGO content were prepared via a simple solvothermal method followed by a high-temperature annealing process in an inert atmosphere. The X-ray diffraction analysis confirmed that the introduction of rGO had no effect on the spinel structure of ZnFeO. In addition, the results of field-emission scanning electron microscopy and (high-resolution) transmission electron microscopy indicated that the synthesized samples had the structure of hollow spheres distributed uniformly onto rGO nanosheets. The diameters of the spheres were determined as about 600-1000 nm. The gas sensing test revealed that the introduction of rGO improved the performance of the sensing of acetone to low concentration, and the ZnFeO/rGO composite gas sensor containing 0.5 wt % of rGO exhibited a high sensitivity in sensing test using 0.8-100 ppm acetone at 200 °C. The response of the 0.5 wt % ZnFeO/rGO sensor to 0.8 ppm acetone was 1.50, and its response to 10 ppm acetone was 8.18, which is around 2.6 times more pronounced than the response of pure ZnFeO (10 ppm, 3.20). Moreover, the sensor showed a wide linear range and good selectivity.
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http://dx.doi.org/10.3762/bjnano.10.242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941408PMC
December 2019

Intermittent vs. continuous vancomycin infusion for gram-positive infections: A systematic review and meta-analysis.

J Infect Public Health 2020 Apr 15;13(4):591-597. Epub 2019 Sep 15.

Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China. Electronic address:

Objective: The clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the effectiveness and safety of IIV and CIV by using a meta-analysis for cohort studies and randomized controlled trials.

Methods: We compared the probabilities of target attainment (PTA) for the measured concentration (C) ≥the target concentration (C), the PTA for the area under the drug concentration curve/minimal inhibitory concentration (AUC/MIC) ≥400, the duration of treatment, nephrotoxicity, and overall mortality after vancomycin treatment as reported in PubMed, Embase, Cochrane, and Web of Science.

Results: A total of 14 studies with 1640 patients were included in the meta-analysis. For IIV, the PTA of C≥C (RR=0.72, 95% CI=0.60-0.88), and nephrotoxicity (RR=1.70, 95% CI=1.34-2.14) were significantly different from those of CIV. The treatment duration (SMD=0.08, 95% CI=-0.08-0.25), the PTA of AUC/MIC ≥ 400 (RR=0.84, 95% CI=0.70-1.00) and mortality (RR=0.94, 95% CI=0.72-1.25) were not significantly different from those of CIV.

Conclusions: The results showed that CIV was easier to achieve C and safer than IIV. Additional randomized controlled trials focusing on the concentration of vancomycin are needed for further analysis.
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http://dx.doi.org/10.1016/j.jiph.2019.09.001DOI Listing
April 2020

Low-dose bisphenol A exposure impairs learning and memory ability with alterations of neuromorphology and neurotransmitters in rats.

Sci Total Environ 2019 Dec 21;697:134036. Epub 2019 Aug 21.

Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China. Electronic address:

To investigate the developmental neurotoxicity of environmental bisphenol A (BPA) exposure for infants and children, postnatal rats were used as the animal model and were divided into four groups. Then, they were treated with different concentrations of BPA (i.e., 0, 0.5, 50, or 5000 μg/kg·bw/day of BPA as the control, low-, medium- and high-exposed group) from postnatal days 7 to 21. Y-maze tests, Golgi-Cox assays and liquid chromatography-tandem mass spectrometry (LC/MS/MS) were performed to test the changes of learning and memory ability, hippocampal neuromorphology and neurotransmitter levels, respectively. The results showed that the BPA-exposed rats, especially the low- and high-exposed rats, needed more trials and longer times to qualify for the learned criterion than the control rats. Additionally, rats after low- or high-exposure to BPA exhibited decreased DG dendritic complexity and reduced CA1 and DG dendritic spine densities in the hippocampus. Low-dosage BPA treatment could significantly alter the neurotransmitter contents in the hippocampus. In male rats, the levels of glutamic acid (Glu) and acetylcholine increased, while the 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) levels decreased, which lead to an unbalanced Glu/GABA ratio. However, in female rats, only 5-HT levels decreased. In conclusion, postnatal exposure to BPA could sex- and dose-dependently disrupt dendritic development and neurotransmitter homeostasis in the rat hippocampus. The impaired spatial learning and memory ability of rats induced by low-dose BPA is associated with both disrupted dendritic development and neurotransmitter homeostasis in the hippocampus.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134036DOI Listing
December 2019

Anti-hypertensive efficacy of amlodipine dosing during morning versus evening: A meta-analysis.

Rev Cardiovasc Med 2019 Jun;20(2):91-98

Department of Pharmacy, the First Hospital of China Medical University, Shenyang 110001, P.R. China.

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.
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http://dx.doi.org/10.31083/j.rcm.2019.02.31814DOI Listing
June 2019

Partial coherence and frustration in self-organizing spherical grids.

Hippocampus 2020 04 24;30(4):302-313. Epub 2019 Jul 24.

SISSA - Cognitive Neuroscience, Trieste, Italy.

Nearby grid cells have been observed to express a remarkable degree of long-range order, which is often idealized as extending potentially to infinity. Yet their strict periodic firing and ensemble coherence are theoretically possible only in flat environments, much unlike the burrows which rodents usually live in. Are the symmetrical, coherent grid maps inferred in the lab relevant to chart their way in their natural habitat? We consider spheres as simple models of curved environments and waiting for the appropriate experiments to be performed, we use our adaptation model to predict what grid maps would emerge in a network with the same type of recurrent connections, which on the plane produce coherence among the units. We find that on the sphere such connections distort the maps that single grid units would express on their own, and aggregate them into clusters. When remapping to a different spherical environment, units in each cluster maintain only partial coherence, similar to what is observed in disordered materials, such as spin glasses.
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http://dx.doi.org/10.1002/hipo.23144DOI Listing
April 2020

Population pharmacokinetics of vancomycin in Chinese patients with augmented renal clearance.

J Infect Public Health 2020 Jan 3;13(1):68-74. Epub 2019 Jul 3.

Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China. Electronic address:

Background: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute has attracted attention widely and in recent years increasing attention has been paid to patients with ARC. A population pharmacokinetic (PPK) analysis was performed to provide a reference for clinical individual therapy of vancomycin in in ARC patients.

Methods: Patients hospitalized in the First Affiliated Hospital of China Medical University from July 2013 to December 2015 and suspected or confirmed infection caused by gram-positive bacteria were enrolled in this study. The serum concentrations were determined by enzyme multiplied immunoassay technique. A nonlinear mixed effects model (NONMEM) was used to evaluate the influence of covariates on vancomycin pharmacokinetics and obtain the PPK model. Bootstrap, visual predictive checks and normalized prediction distribution errors were used to evaluate the estabolishe model.

Results: A total of 186 vancomycin serum samples from 95 patients, including 24 females and 71 males were studied. The final model was as follows: [Formula: see text] and [Formula: see text] . The final PPK model in ARC patients was proved to be robust and reliable. Age was identified as the most significant covariate in the final model.

Conclusions: In this study, a simple population pharmacokinetic (PPK) model of vancomycin in Chinese patients with ARC was established using a nonlinear mixed-effects model (NONMEM). The final PPK model could achieve a good predictive effect, which provides a reference for clinical individual therapy.
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http://dx.doi.org/10.1016/j.jiph.2019.06.016DOI Listing
January 2020

Improved Efficiency of the Desulfurization of Oil Sulfur Compounds in Escherichia coli Using a Combination of Desensitization Engineering and DszC Overexpression.

ACS Synth Biol 2019 06 7;8(6):1441-1451. Epub 2019 Jun 7.

Guangdong Key Laboratory of Fermentation and Enzyme Engineering, Guangdong Research Center of Industrial Enzyme and Green Manufacturing Technology, School of Biology and Biological Engineering , South China University of Technology , Guangzhou 510006 , China.

The 4S pathway of biodesulfurization, which can specifically desulfurize aromatic S-heterocyclic compounds without destroying their combustion value, is a low-cost and environmentally friendly technology that is complementary to hydrodesulfurization. The four Dsz enzymes convert the model compound dibenzothiophene (DBT) into the sulfur-free compound 2-hydroxybiphenyl (HBP). Of these four enzymes, DszC, the first enzyme in the 4S pathway, is the most severely affected by the feedback inhibition caused by HBP. This study is the first attempt to directly modify DszC to decrease its inhibition by HBP, with the results showing that the modified protein is insensitive to HBP. On the basis of the principle that the final HBP product could show a blue color with Gibbs reagent, a high-throughput screening method for its rapid detection was established. The screening method and the combinatorial mutagenesis generated the mutant AKWC (A101K/W327C) of DszC. After the IC was calculated, the feedback inhibition of the AKWC mutant was observed to have been substantially reduced. Interestingly, the substrate inhibition of DszC had also been reduced as a result of directed evolution. Finally, the recombinant BL21(DE3)/BADC*+C* (C* represents AKWC) strain exhibited a specific conversion rate of 214.84 μmol/g/h, which was 13.8-fold greater than that of the wild-type strain. Desensitization engineering and the overexpression of the desensitized DszC protein resulted in the elimination of the feedback inhibition bottleneck in the 4S pathway, which is practical and effective progress toward the production of sulfur-free fuel oil. The results of this study demonstrate the utility of desensitization of feedback inhibition regulation in metabolic pathways by protein engineering.
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http://dx.doi.org/10.1021/acssynbio.9b00126DOI Listing
June 2019

[Simultaneous determination of five neurotransmitters in neonatal rat hippocampus by adding vitamin C coupled with isotope dilution-ultra-high performance liquid chromatography-tandem mass spectrometry].

Se Pu 2019 Apr;37(4):404-411

Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China.

Analysis of neurotransmitters in brain tissue is useful for mechanistic studies of the central nervous system. Isotope dilution coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of glutamic acid, -amino butyric acid, acetylcholine, dopamine, and serotonin in the hippocampus tissue. A 2% (v/v) acetic acid in water-methanol (9:1, v/v) solution was used to prepare the standards and re-dissolute samples after nitrogen drying. An Ultimate AQ-C column (150 mm×4.6 mm, 3 μm) was used as the analytical column and 0.1% (v/v) formic acid in water and methanol were used as the mobile phase. Gradient elution was performed and all target compounds were eluted over 3 min at 28℃. Vitamin C spiked during the sample pretreatment and storage periods significantly retarded the oxidation of dopamine and serotonin and improved the neurotransmitter stability. The developed method showed good linearities (correlation coefficient ()>0.998), low detection limits (0.15-1.0 μg/L), good inter-and intra-day precisions (relative standard deviations:0.39%-13.6%), good accuracy (92.9%-119%), low carry-over, and excellent stability. Moreover, the method was successfully applied and validated in the determination of rat hippocampus exposed to bisphenol A.
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http://dx.doi.org/10.3724/SP.J.1123.2018.11012DOI Listing
April 2019

Thermosynechococcus as a thermophilic photosynthetic microbial cell factory for CO utilisation.

Bioresour Technol 2019 Apr 22;278:255-265. Epub 2019 Jan 22.

School of Environment and Energy, Peking University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address:

Thermophilic unicellular cyanobacterium Thermosynechococcus elongatus PKUAC-SCTE542, has been developed as a thermophilic photosynthetic microbial cell factory for CO utilisation. The strain exhibits its highest growth rate around 55 °C, can withstand up to 15% CO, and up to 0.5 M concentration of sodium bicarbonate. The strain is also capable of resisting a 200 ppm concentration of NO and SO in simulated flue gasses, and these compounds have a positive effect on its growth. Whole genome sequencing of the strain revealed the presence of numerous forms of active transport of nutrients and additional chaperones acting as the predominant mechanism of strain adaptation to high temperatures. Based on the sequenced genome, two neutral gene insertion sites have been identified and engineered using modular vectors. Site-specific knock-ins and knock-outs have been performed using the spectinomycin resistance gene and proved functional, enabling future application of the strain to produce biofuels and biochemicals from waste CO.
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http://dx.doi.org/10.1016/j.biortech.2019.01.089DOI Listing
April 2019

Graphene-enhanced metal oxide gas sensors at room temperature: a review.

Beilstein J Nanotechnol 2018 9;9:2832-2844. Epub 2018 Nov 9.

College of Mechanical Engineering, Yangzhou University, Yangzhou 225127, China.

Owing to the excellent sensitivity to gases, metal-oxide semiconductors (MOS) are widely used as materials for gas sensing. Usually, MOS gas sensors have some common shortages, such as relatively poor selectivity and high operating temperature. Graphene has drawn much attention as a gas sensing material in recent years because it can even work at room temperature, which reduces power consumption. However, the low sensitivity and long recovery time of the graphene-based sensors limit its further development. The combination of metal-oxide semiconductors and graphene may significantly improve the sensing performance, especially the selectivity and response/recovery rate at room temperature. In this review, we have summarized the latest progress of graphene/metal-oxide gas sensors for the detection of NO, NH, CO and some volatile organic compounds (VOCs) at room temperature. Meanwhile, the sensing performance and sensing mechanism of the sensors are discussed. The improved experimental schemes are raised and the critical research directions of graphene/metal-oxide sensors in the future are proposed.
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http://dx.doi.org/10.3762/bjnano.9.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244217PMC
November 2018

Temperature-controlled thermophilic bacterial communities in hot springs of western Sichuan, China.

BMC Microbiol 2018 10 17;18(1):134. Epub 2018 Oct 17.

School of Environment and Energy, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

Background: Ganzi Prefecture in Western China is situated geographically at the transition regions between Tibetan Plateau and Sichuan Basin in a highly tectonically active boundary area between the India and Eurasia plates. The region hosts various hot springs that span a wide range of temperature from 30 to 98 °C and are located at high altitude (up to 4200 m above sea level) in the region of large geothermal anomalies and active Xianshuihe slip-fault that has been active since Holocene. The site represents a biodiversity reservoir for thermophiles, yet their diversity and relationship to geochemical parameters are largely unknown. In the present work, bacterial diversity and community structure in 14 hot springs of Ganzi were investigated using Illumina MiSeq sequencing.

Results: Bacterial community compositions were evidently distinct among the 14 hot springs, and the bacterial communities in hot springs were majorly abundant in phyla Aquificae, Cyanobacteria and Proteobacteria. Both clustering and PCoA analysis suggested the existence of four bacterial community patterns in these hot springs. Temperature contributed to shaping bacterial community structure of hot springs as revealed by correlation analysis. Abundant unassigned-genus sequences detected in this study strongly implied the presence of novel genera or genetic resources in these hot springs.

Conclusion: The diversity of hot springs of Ganzi prefecture in Western Sichuan, China is evidently shaped by temperature. Interestingly disproportionally abundant unassigned-genus sequences detected in this study show indicate potential of novel genera or phylotypes. We hypothesize that frequent earthquakes and rapidly changing environment might have contributed to evolution of these potentially new lineages. Overall, this study provided first insight into the bacterial diversity of hot springs located in Western Sichuan, China and its comparison with other similar communities worldwide.
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http://dx.doi.org/10.1186/s12866-018-1271-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191902PMC
October 2018

Textile Dye Decolorizing Synechococcus PCC7942 Engineered With CotA Laccase.

Front Bioeng Biotechnol 2018 12;6:95. Epub 2018 Jul 12.

School of Environment and Energy, Shenzhen Graduate School, Peking University, Shenzhen, China.

Cyanobacteria are prokaryotic phototrophs capable of achieving high cellular densities with minimal inputs. These prokaryotic organisms can grow using sunlight as energy source and carbon dioxide as carbon source what makes them promising candidates as microbial cell factories for the production of numerous compounds such as chemicals, fuels, or biocatalysts. In this study, we have successfully designed and constructed using synthetic biology approach two recombinant strains of PCC7942 for heterologous expression of the industrially relevant CotA laccase. One of the strains (PCC7942-NSI-CotA) was constructed through integration of the laccase gene into neutral site I of the cyanobacterial genome whilst the other (PCC7942-NSII-CotA) targeted neutral site II of the genome. Of the two strains the one with CotA laccase integrated in neutral site II (PCC7942-NSII-CotA) was superior in terms of growth rate and enzymatic activity toward typical laccase substrates: ABTS [2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonate)] and syringaldazine. That may suggest that two of the traditionally used neutral sites of PCC7942 are not equally suitable for the expression of certain transgenes. The PCC7942-NSII-CotA produced protein was capable of decolourising three classes of dyes namely: anthraquinonic-, azo-, and indigoid-type over 7 days of incubation making the strain a potentially useful microbial cell factory for the production of broad-spectrum biodegradation agent. Interestingly, presence of additional synthetic redox mediator ABTS had no effect on the degradation of these dyes.
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http://dx.doi.org/10.3389/fbioe.2018.00095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052094PMC
July 2018

Application of vancomycin in patients with varying renal function, especially those with augmented renal clearance.

Pharm Biol 2016 Dec 1;54(12):2802-2806. Epub 2016 Jun 1.

a Department of Pharmacy , the First Affiliated Hospital of China Medical University , Shenyang , China.

Context: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute, and has attracted wide attention in recent years.

Objective: This study evaluates the effects of ARC on serum vancomycin concentration in patients administered vancomycin.

Materials And Methods: This was a retrospective study in patients receiving vancomycin treatment at a dose of 1000 mg in every 12 h and undergoing serum monitoring admitted over a 2-year period (May 2013 to May 2015), in order to estimate the influence of ARC on serum vancomycin concentration. In this study, statistical comparisons were made on the results from patients grouped according to creatinine clearance (CL).

Results: One hundred forty-eight patients were enrolled in our study. The results showed that ARC patients were significantly younger, with a significantly lower S and higher GFR. The CL and steady-state trough concentrations of serum vancomycin exhibited a logarithmic correlation (Rs = -0.699, R=0.488, p < 0.01) in the patients included in our study. The trough vancomycin concentrations of 62.9% patients in high CL group were under 10 μg/mL.

Discussion And Conclusion: Since ARC was significantly associated with subtherapeutic serum vancomycin concentration, it was necessary to devise adjusted dosage regimens for these patients based on their CL.
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http://dx.doi.org/10.1080/13880209.2016.1183684DOI Listing
December 2016

An Interactive Astronaut-Robot System with Gesture Control.

Comput Intell Neurosci 2016 11;2016:7845102. Epub 2016 Apr 11.

School of Computing, University of Portsmouth, Portsmouth, Hampshire PO1 3HE, UK.

Human-robot interaction (HRI) plays an important role in future planetary exploration mission, where astronauts with extravehicular activities (EVA) have to communicate with robot assistants by speech-type or gesture-type user interfaces embedded in their space suits. This paper presents an interactive astronaut-robot system integrating a data-glove with a space suit for the astronaut to use hand gestures to control a snake-like robot. Support vector machine (SVM) is employed to recognize hand gestures and particle swarm optimization (PSO) algorithm is used to optimize the parameters of SVM to further improve its recognition accuracy. Various hand gestures from American Sign Language (ASL) have been selected and used to test and validate the performance of the proposed system.
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http://dx.doi.org/10.1155/2016/7845102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842936PMC
December 2016

Clinicopathologic characteristics and prognosis of Borrmann type IV gastric cancer: a meta-analysis.

World J Surg Oncol 2016 Feb 24;14(1):49. Epub 2016 Feb 24.

Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China.

Background: The clinicopathologic features and surgical treatment strategy of Borrmann type IV (B-4) gastric cancer remains controversial. This meta-analysis was conducted to evaluate the clinicopathologic features of patients with B-4 gastric cancer and to assess whether or not non-curative resection improved prognosis.

Methods: PubMed and Embase were searched for relevant articles. Statistical analysis was performed using RevMan (version 5.2). The odds ratio (OR), risk ratio (RR), hazard ratio (HR) with 95% confidence interval (CI), and weighted average of median survival times were calculated as effect values.

Results: Fifteen studies were included. Compared with Borrmann type "others" (B-O), B-4 had a higher incidence of poorly differentiated carcinoma (OR=4.92; 95% CI=3.10-7.83; P<0.01), lymph node metastases (OR=2.13; 95% CI=1.88-2.41; P<0.01), peritoneal metastases (OR=3.91; 95% CI=3.37-4.54; P<0.01), serosal invasion (OR=3.66; 95% CI=2.91-4.60; P<0.01), and lymphatic invasion (OR=1.39; 95% CI=1.02-1.91; P=0.04). B-4 patients with non-curative resection were associated with a worse survival rate (HR=2.83; 95% CI=2.35-3.40; P<0.01) than patients with curative resection; however, B-4 patients with non-curative resection had a better survival rate (1-year: RR=0.70, 95% CI=0.63-0.77; P<0.01; 2-year: RR=0.90, 95% CI=0.85-0.94; P<0.01) than patients with non-resection.

Conclusions: Our meta-analysis indicated that B-4 patients were associated with poor tumor differentiation, lymph node metastases, peritoneal metastases, serosal invasion, lymphatic invasion, and prognosis. Curative resection may increase the survival rate for B-4 patients. If it is not possible to perform a curative resection, a non-curative resection may improve the prognosis.
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http://dx.doi.org/10.1186/s12957-016-0805-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765022PMC
February 2016

Polymorphism in epidermal growth factor is related to clinical outcomes of metastatic colorectal cancer patients treated with cetuximab: a systematic review and meta-analysis.

Int J Clin Exp Med 2015 15;8(7):10929-37. Epub 2015 Jul 15.

Department of Surgical Oncology and General Surgery, First Hospital of China Medical University Shenyang, China.

Numerous studies focusing on genetic variants in order to find cetuximab subpopulation biomarkers have emerged, yet the significance of each biomarker is diverse. Based on these results, we carried out a meta-analysis to assess the correlation between epidermal growth factor (EGF) A61G polymorphism and clinical outcomes of metastatic colorectal cancer (mCRC) patients treated with cetuximab. We aim to prove that EGF polymorphisms may be potential biomarkers for cetuximab therapeutic strategies. We identified 6 previously published studies including 569 patients treated with cetuximab-based regimens. Outcomes included clinical response, progression-free survival (PFS), and overall survival (OS). GG homozygote showed association with better response rates (GG vs. AA+AG, OR = 2.82; 95% CI = 1.58-5.04) and than AA+AG genotypes. This meta-analysis showed that mCRC patients harboring GG genotype of EGF A61G polymorphism inclined to have a better response rate with cetuximab treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565270PMC
September 2015

[Development of ultrasonic power meter].

Zhongguo Yi Liao Qi Xie Za Zhi 2014 Jul;38(4):259-60, 281

This article describes the design and development of an ultrasonic power meter which is consist of an electronic balance, a practice target, an acoustic enclosures and a blocking. The electronic balance mounted on the blocking is linked with the practice target by connecting rod. By adjusting the blocking makes the practice target suspended above ultrasound probe, and then the ultrasonic power can be measured. After initial tests, the ultrasonic power meter performanced with good stability and high precision.
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July 2014

Poly[(acetato-κ(2)O,O')aqua-(μ(4)-1H-benzimidazole-5,6-dicarboxyl-ato-κ(6)N(3):O(5),O(5'):O(5),O(6):O(6'))cerium(III)].

Acta Crystallogr Sect E Struct Rep Online 2012 May 25;68(Pt 5):m673. Epub 2012 Apr 25.

School of Chemistry and Environment, South China Normal University, Guangzhou 510006, People's Republic of China.

In the title compound, [Ce(C(9)H(4)N(2)O(4))(C(2)H(3)O(2))(H(2)O)](n), the Ce(III) ion is coordinated by five O atoms and one N atom from four 1H-benzimidazole-5,6-dicarboxyl-ato (L) ligands and by two O atoms from an acetate ligand and one aqua ligand, forming a slightly distorted tricapped trigonal-prismatic geometry. The L ligands are bridging, forming a layered polymer parallel to (010). In the crystal, O-H⋯O and N-H⋯O hydrogen bonds connect the polymer layers into a three-dimensional network.
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http://dx.doi.org/10.1107/S1600536812017503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344394PMC
May 2012

Poly[(μ-1H-benzimidazole-5,6-dicarboxyl-ato)lead(II)].

Acta Crystallogr Sect E Struct Rep Online 2011 Jun 14;67(Pt 6):m755. Epub 2011 May 14.

School of Chemistry and Environment, South China Normal University, Guangzhou 510006, People's Republic of China.

The crystal structure of the two-dimensional polymeric title compound, [Pb(C(9)H(4)N(2)O(4))](n), comprises one crystallo-graphic-ally independent Pb(II) atom and one fully deprotonated 1H-benzimidazole-5,6-dicarboxyl-ate (H(2)L) ligand. The Pb(II) atom is seven-coordinated by six O atoms and one N atom from the H(2)L ligands, giving a capped octa-hedral coordination geometry. The structure is a layered two-dimensional coordination polymer extending parallel to (100) with N-H⋯O hydrogen bonds inter-actions between the layers, stabilizing the crystal structure.
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http://dx.doi.org/10.1107/S1600536811017065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120506PMC
June 2011

Sonodynamic and photodynamic therapy in advanced breast carcinoma: a report of 3 cases.

Integr Cancer Ther 2009 Sep;8(3):283-7

Chemistry and Environment College, Southern China Normal University, Guangzhou, People's Republic of China.

Photodynamic therapy (PDT) is an established therapeutic method, first approved by the FDA for certain kinds of cancer in 1998. There are also increasing data to show that a related procedure, sonodynamic therapy (SDT), is a promising new modality for cancer treatment. Here, the authors report clinical results in 3 advanced refractory breast cancer patients who were treated using a combination of sonodynamic and photodynamic therapy (SPDT), along with conventional therapies. All 3 patients had pathologically proven metastatic breast carcinoma. These widely disseminated carcinomas had ultimately failed to respond to conventional therapy. A new sensitizing agent, Sonoflora 1 (SF1) was administered sublingually; then, after a 24-hour delay, patients were treated with a combination of light and ultrasound. All patients had significant partial or complete responses. SPDT is a promising new therapeutic combination for the treatment of breast cancer.
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http://dx.doi.org/10.1177/1534735409343693DOI Listing
September 2009