Publications by authors named "Xuemei Yao"

32 Publications

Spatiotemporal Dynamics of Affective and Semantic Valence Among Women.

Front Hum Neurosci 2021 13;15:602192. Epub 2021 Jul 13.

Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi'an, China.

As an important dimension of emotional assessment, valence can refer to affective valence reflecting an emotional response, or semantic valence reflecting knowledge about the nature of a stimulus. A previous study has used repeated exposure to separate these two similar cognitive processes. Here, for the first time, we compared the spatiotemporal dynamics of the affective and semantic modes of valence by combining event-related potentials with repeated exposure. Forty-seven female participants were assigned to the feeling-focused and semantic-focused groups and thereafter repeatedly viewed the pictures selected for the study. Self-report behavioral results showed that post-test scores were significantly lower than pre-test scores in the feeling-focused group, while the differences between the two tests were not significant in the semantic-focused group. At the neural level, N2 amplitudes decreased and early late positive potential amplitudes increased in both groups, suggesting that the participants perceived the repeated pictures more fluently and retrieved the traces of the stimulus spontaneously regardless of the valence they judged. However, the late positive potential amplitudes in anterior areas and the activity of the middle frontal gyrus were attenuated in the feeling-focused group; however, this component in posterior areas and the activity of the precentral gyrus were increased in the semantic-focused group. Therefore, the processes of affective and semantic valence are similar in the early stages of image perception and retrieval, while in the later stage of valence judgment, these processes show different brain activation patterns. The results provide electrophysiological evidence for the differences in psychological processes when judging the two modes of valence.
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http://dx.doi.org/10.3389/fnhum.2021.602192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315150PMC
July 2021

Enhanced isomerization of rare sugars by ribose-5-phosphate isomerase A from Ochrobactrum sp. CSL1.

Enzyme Microb Technol 2021 Aug 26;148:109789. Epub 2021 Mar 26.

School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou, 215009, PR China. Electronic address:

Ribose-5-phosphate isomerase A (RpiA) is of great importance in biochemistry research, however its application in biotechnology has not been fully explored. In this study the activity of RpiA from Ochrobactrum sp. CSL1 (OsRpiA) towards D-allose was engineered based on sequential and structural analyses. Strategies of alanine scanning, rational design and saturated mutagenesis were employed to create three mutant libraries. A single mutant of K124A showed a 45 % activity improvement towards D-allose. The reaction properties of the mutant were analyzed, and a shift of optimal pH and higher thermal stability at low reaction temperatures were identified. The conversion of D-allose was also improved by 40 % using K124A, and higher activities on major substrates were found in the mutant's substrate scope, implying its application potential in rare sugar preparation. Kinetics analysis revealed that K of K124A mutant decreased by 12 % and the catalytic efficiency increased by 65 % towards D-allose. Moreover, molecular dynamics simulation illustrated the binding of substrate and K124A was more stable than that of the wild-type. The shorter distance and more relax bond angle between the catalytic residue of K124A and D-allose explained the activity improvement in detail. This study highlights the potential of OsRpiA as a biocatalyst for rare sugar preparation, and provides distinct evidences for its catalytic mechanism.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109789DOI Listing
August 2021

HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications.

Cell Rep 2020 12;33(10):108487

School of Life Science, Chongqing University, Chongqing 400044, China. Electronic address:

Ferroptosis is a recently discovered form of programed cell death caused by the metabolically regulated lipid peroxidation and holds promise for cancer treatment, but its regulatory mechanisms remain elusive. In this study, we observe that lactate-rich liver cancer cells exhibit enhanced resistance to the ferroptotic damage induced by common ferroptosis inducers such as Ras-selective lethal small molecule 3 (RSL3) and Erastin and that the monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids. Additionally, blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. In vitro and in vivo evidence confirms that lactate regulates the ferroptosis of HCC cells and highlights its translational potential as a therapeutic target for ferroptosis-based tumor treatment.
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http://dx.doi.org/10.1016/j.celrep.2020.108487DOI Listing
December 2020

Unique regulator SrpR mediates crosstalk between efflux pumps TtgABC and SrpABC in Pseudomonas putida B6-2 (DSM 28064).

Mol Microbiol 2021 01 6;115(1):131-141. Epub 2020 Oct 6.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

The coexistence of multiple homologous resistance-nodulation-division (RND) efflux pumps in bacteria is frequently described with overlapping substrate profiles. However, it is unclear how bacteria balance their transcription in response to the changing environment. Here, we characterized a repressor, SrpR, in Pseudomonas putida B6-2 (DSM 28064), whose coding gene is adjacent to srpS that encodes the local repressor of the RND-type efflux pump SrpABC gene cluster. SrpR was demonstrated as a specific repressor of another RND efflux pump gene cluster ttgABC that is locally repressed by TtgR. SrpR was found to be capable of binding to the ttgABC operator with a higher affinity (K , 138.0 nM) compared to TtgR (K , 15.4 μM). EMSA and β-galactosidase assays were performed to survey possible effectors of SrpR with 35 available chemicals being tested. Only 2,3,4-trichlorophenol was identified as an effector of SrpR. A regulation model was then proposed, representing a novel strategy for balancing the efflux systems with partially overlapping substrate profiles. This study highlights sophisticated interactions among the RND efflux pumps in a Pseudomonas strain, which may endow bacteria with certain advantages in a fluctuant environment.
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http://dx.doi.org/10.1111/mmi.14605DOI Listing
January 2021

Relationship of vitamin D receptor gene polymorphism with sarcopenia and muscle traits based on propensity score matching.

J Clin Lab Anal 2020 Nov 22;34(11):e23485. Epub 2020 Jul 22.

Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, China.

Background: Vitamin D receptor (VDR) gene polymorphism is reported to be associated with muscle mass and muscle strength. Loss of skeletal muscle mass and decreased muscle strength are the main characteristics of sarcopenia. In this study, the relationship of VDR gene polymorphism with muscle traits (muscle mass, muscle strength, and physical performance) and sarcopenia were studied in Xinjiang, China.

Methods: Totally, 205 sarcopenia patients were enrolled. Propensity score method was used to match control group. FokI and BsmI polymorphisms were genotyped using improved multiplex ligation detection reaction (iMLDR).

Results: Fok1, but not Bsm1, polymorphism was significantly associated with sarcopenia. Patients with Fok1 GG genotype were more likely to have sarcopenia. Both Bsm1 and Fok1 polymorphism were related to muscle traits. Patients with Bsm1 CT genotype had lower gait speed (GS) but higher skeletal mass index. Patients with Fok1 GG genotype had lower GS, and female subjects with the Fok1 GG genotype had lower handgrip strength (HS). GS was decreased in Bsm1 CT genotype than CC carriers. HS and GS were decreased in Fok1 GG genotype than AA carriers.

Conclusion: Fok1, but not Bsm1, polymorphism is associated with sarcopenia. Both Bsm1 and Fok1 polymorphism affect both HS and GS.
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http://dx.doi.org/10.1002/jcla.23485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676216PMC
November 2020

Citral-loaded chitosan/carboxymethyl cellulose copolymer hydrogel microspheres with improved antimicrobial effects for plant protection.

Int J Biol Macromol 2020 Dec 18;164:986-993. Epub 2020 Jul 18.

School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, China. Electronic address:

The extensive use of chemical pesticides in agricultural production has caused great damage to the soil and ecological environment. Citral, a monoterpene aldehyde, has been shown to inhibit the growth of a variety of pathogenic fungi by affecting mitochondrial structure. However, the high volatility and chemical instability of citral may restrict its applications in the agricultural industries. In this study, a concise and facile method for the preparation of modified copolymer chitosan/carboxymethyl cellulose (CS/CMC) hydrogels microspheres loaded with citral was developed to increase and stabilize the bioavailability of this natural bioactive substance. Polyelectrolyte composite scaffold hydrogel microspheres were synthesized by polycationic chitosan (CS) and polyanionic carboxymethyl (CMC). Citral was embedded into the microspheres by coupling the carbonyl group of citral with the amino group of CS to form a Schiff base structure. The effects of three parameters including CS/CMC weight ratio, concentration of CMC and citral on the loading ratio were investigated and optimal loading of 68% was achieved based on single-factor experiments. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were employed to confirm and characterize the structure and surface morphology of the microspheres. Both the XRD and FTIR spectra indicated that the microspheres contain -C=N- covalent bonds between CS and citral. The hydrogel microspheres with incorporated citral exhibited effective and improved in vitro antibacterial effects against E. coli, S. aureus and B. subtilis than non-loaded CS microspheres. Moreover, CS/CMC-citral-MPs showed a good antifungal effect in vivo in reducing disease incidence caused by the plant pathogenic fungus Botrytis cinerea in Solanum lycopersicum. Different from the previous applications of CS and citral in the preservation of picked fruits, citral was embedded into CS/CMC microspheres to achieve improved plant protection against Botrytis cinerea. The microspheres are a promising green antimicrobial agent against plant pathogens in crop protection and other fields.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.164DOI Listing
December 2020

Exploring Multifunctional Residues of Ribose-5-phosphate Isomerase B from sp. CSL1 Enhancing Isomerization of d-Allose.

J Agric Food Chem 2020 Mar 9;68(11):3539-3547. Epub 2020 Mar 9.

School of Chemistry, Biology, and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, P.R. China.

Ribose-5-phosphate isomerase B is of great importance for biocatalysis and biosynthesis, but the multifunctional residues in active sites hinder the research efforts. This study employed rational design strategies to locate the key residues of RpiB from sp. CSL1 (OsRpiB). A single-mutant S9T of a noncontact residue showed 80% activity improvement toward d-allose. A double-mutant S98H/S134H further increased the activity to 3.6-fold. The mutations were analyzed by kinetics and molecular dynamics analyses, indicating that S9T might enhance the substrate binding and catalysis by inducing a steric effect, and S98H/S134H could strengthen both ring opening and binding of d-allose. Though S98H/S134H showed low temperature stability, its potential was explored by isomerizing d-allose to d-psicose with higher conversion and in less reaction time. The findings of this study were beneficial for illustrating the complex functions of key residues in RpiBs and applying OsRpiB in preparing rare sugars.
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http://dx.doi.org/10.1021/acs.jafc.9b07855DOI Listing
March 2020

Comparison of revised EWGSOP criteria and four other diagnostic criteria of sarcopenia in Chinese community-dwelling elderly residents.

Exp Gerontol 2020 02 6;130:110798. Epub 2019 Dec 6.

School of Public Health, Xinjiang Medical University, Xinjiang, Urumqi, China. Electronic address:

Objectives: To compare the prevalence and associated factors of sarcopenia defined by the revised European Working Group on Sarcopenia in Older People (EWGSOP2) criteria with the initial European Working Group on Sarcopenia in Older People (EWGSOP1) criteria, the Asia Working Group for Sarcopenia (AWGS), the International Working Group on Sarcopenia (IWGS), and the National Institutes of Health (FNIH) Sarcopenia Project criteria among Chinese community-dwelling older adults.

Design: A cross-sectional study.

Setting: Two community health centers in Urumqi, China.

Participants: A total of 483 participants aged 60 years and older from the community.

Measurement: Anthropometry, skeletal muscle mass, handgrip strength, 4-m walking speed, and biochemical markers. Questionnaire collected information included demographics, lifestyle, and quality of life.

Results: The prevalence of EWGSOP2-defined sarcopenia (men: 6.5%; women: 3.3%) was lower than that defined by the EWGSOP1 (men: 22.3%; women 11.7%), AWGS (men: 10.9%; women: 8.0%), and IWGS (men: 24.5%; women: 11.0%) criteria, but higher than FNIH criteria (men: 6.0%; women: 1.7%). The positive percent agreement was lower (men: 15.6%-63.6%; women: 15.2%-40.0%), while negative percent agreement was higher (men: 96.4%-100.0%; women: 97.3%-99.6%). Sex (OR 0.31, 95% CI 0.12-0.81), education level (OR 0.49, 95% CI 0.29-0.83), and body mass index (BMI, OR 0.73, 95% CI 0.62-0.86) were associated with sarcopenia defined by the EWGSOP2 criteria. No consistent pattern of risk factors associated with sarcopenia in EWGSOP2 and four other diagnostic criteria was present.

Conclusions And Implications: The EWGSOP2 criteria did not agree with the EWGSOP1, AWGS, IWGA, and FNIH criteria defining sarcopenia. Risk factors associated with the EWGSOP2-defined sarcopenia have no consistent patterns with the EWGSOP1, AWGS, IWGA, and FNIH criteria. Therefore, the validity of the EWGSOP2 consensus needs to be confirmed in further prospective studies.
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http://dx.doi.org/10.1016/j.exger.2019.110798DOI Listing
February 2020

Psychometric Properties of the Effort-Reward Imbalance Questionnaire for Teachers (Teacher ERIQ).

Front Psychol 2019 12;10:2047. Epub 2019 Sep 12.

MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, China.

The effort-reward imbalance (ERI) model is a theoretical model of a psychosocial work environment with adverse effects on health and well-being that focuses on a mismatch between high efforts spent and low rewards received at work. This study aimed to develop and psychometrically test an effort-reward imbalance questionnaire for teachers (Teacher ERIQ) based on the ERI model. The structure validity, reliability, and criterion validity of the new questionnaire's scores were evaluated in a sample of 475 Chinese teachers. The results of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) showed that a structure of four factors of effort (workload, emotional demands, student-related issues, and social responsibility) and two factors of reward (emotional reward and material reward) in accordance with the ERI model had significant factor loadings and acceptable model fit. The Cronbach's Alpha coefficients of all dimensions' scores showed that the questionnaire scores had good reliability. Criterion validity was indicated by significant correlation coefficients of scores of most dimensions along with teachers' self-reported job burnout and non-reciprocal social relations, as well as the ANOVA results showing that the differences of the scores of the two criterion scales in different ERI ratio levels were significant. The results also showed that teacher's ERI level varied with demographic variables such as age, gender and school type. The Teacher ERIQ is a valid and reliable new measurement for assessing teachers' psychosocial work characteristics. It can be an important tool to provide new explanations of stress-related health risks among teachers and to guide the development of preventive measurements.
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http://dx.doi.org/10.3389/fpsyg.2019.02047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751258PMC
September 2019

Two classes of cytochrome P450 reductase genes and their divergent functions in Camptotheca acuminata Decne.

Int J Biol Macromol 2019 Oct 24;138:1098-1108. Epub 2019 Jul 24.

School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, China. Electronic address:

Cytochrome P450 monooxygenases (CYP450s) and their auxiliary cytochrome P450 reductases (CPRs) are important and commonly involved in the biosynthesis of camptothecin (CPT). To better understand the possible functions of CPRs in planta, we first isolated two CaCPRs genes from Camptotheca acuminata. Sequence analysis revealed the presence of common conserved FMN-, FAD- and NADPH-binding motifs in putative CaCPR1/CaCPR2 proteins. The two CaCPR paralogs were assigned to the Class I and Class II of CPRs, respectively, according to phylogenetic tree. The recombinant CrCYP72-CaCPR1 and CrCYP72-CaCPR2 enzymes and their substrate bioconversion rates of 23.09% and 35.23% demonstrated that both CaCPRs could support the enzyme activities of CrSLS1. Gene silencing of CaCPRs by VIGS led to downregulation of CaCPR1/CaCPR2 expression by 50-67%, accompanied with 10-15% slight decrease and 57-63% dramatic reduction for CaCPR1 and CaCPR2 individually in CPT accumulations. Moreover, CaCPR1/CaCPR2 displayed almost omnipresent expression patterns across Camptotheca tissues. While in comparison to constitutive expression of CaCPR1 gene, CaCPR2 and CYP450 genes were all dramatically phytohormone-induced expressed in leaves which were main tissues for isoprenoid and CPT biosynthesis. Our results suggested that, in Camptotheca seedlings, CaCPR2 had a distinct function from CaCPR1 that was clearly involved in the inducible specialized metabolism for CPT biosynthesis.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.07.141DOI Listing
October 2019

Characterization of Ribose-5-Phosphate Isomerase B from Newly Isolated Strain sp. CSL1 Producing -Rhamnulose from -Rhamnose.

J Microbiol Biotechnol 2018 Jul;28(7):1122-1132

School of Chemistry, Biology, and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, P.R. China.

In this study, we attempted to find new and efficient microbial enzymes for producing rare sugars. A ribose-5-phosphate isomerase B (OsRpiB) was cloned, overexpressed, and preliminarily purified successfully from a newly screened sp. CSL1, which could catalyze the isomerization reaction of rare sugars. A study of its substrate specificity showed that the cloned isomerase (OsRpiB) could effectively catalyze the conversion of -rhamnose to -rhamnulose, which was unconventional for RpiB. The optimal reaction conditions (50°C, pH 8.0, and 1 mM Ca) were obtained to maximize the potential of OsRpiB in preparing -rhamnulose. The catalytic properties of OsRpiB, including , , and catalytic efficiency (/), were determined as 43.47 mM, 129.4 sec, and 2.98 mM/sec. The highest conversion rate of -rhamnose under the optimized conditions by OsRpiB could reach 26% after 4.5 h. To the best of our knowledge, this is the first successful attempt of the novel biotransformation of -rhamnose to -rhamnulose by OsRpiB biocatalysis.
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http://dx.doi.org/10.4014/jmb.1802.02021DOI Listing
July 2018

PI3K signaling pathways modulated white spot syndrome virus (WSSV) replication in Procambarus clarkii.

Fish Shellfish Immunol 2018 May 26;76:279-286. Epub 2018 Feb 26.

Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), Yantai, 264003, Shandong, China. Electronic address:

The PI3K/AKT signaling pathway is commonly exploited to regulate viral replication and affect the fate of infected cells. In the present study, a PI3K-specific inhibitor (LY294002) was employed to pretreat crayfish to evaluate the effects of PI3K/AKT signaling pathway in WSSV replication. The results showed that the WSSV copy numbers in crayfish pretreated with LY294002 were significantly lower than those in Tris-HCl pretreatment crayfish on the sixth and tenth day after WSSV infection. In semigranular cells, the apoptosis rates were up-regulated on the third day post-WSSV infection, and a significantly lower proportion of apoptosis cells were observed in LY294002-pretreatment group. The expression level of Bax, Bax inhibitor-1 and lectin mRNA in haemocytes of crayfish were increased after WSSV infection. After the secondary stimulation with Tris-HCl, the Bax expression level in LY294002-pretreatment crayfish was significantly higher than that of crayfish pretreated with Tris-HCl on the third or sixth day, but the Toll and lectin mRNA expression decreased significantly on the third, sixth and tenth day. The Bax mRNA expression levels in LY294002-WSSV group were significantly higher than those in Tris-HCl-WSSV group on the third and tenth day. The Bax inhibitor-1 mRNA expression levels in LY294002-WSSV group were significantly lower than those in Tris-HCl-WSSV crayfish on the third day. These results together indicated that the hosts PI3K/AKT signaling pathway play positive roles in WSSV replication through the balance between host cell apoptois and innate immune responses. This information is helpful to further understand the role of PI3K/AKT signaling pathway on WSSV replication in Decapoda crustaceans.
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http://dx.doi.org/10.1016/j.fsi.2018.02.045DOI Listing
May 2018

Multiple Roles for Two Efflux Pumps in the Polycyclic Aromatic Hydrocarbon-Degrading Pseudomonas putida Strain B6-2 (DSM 28064).

Appl Environ Microbiol 2017 Dec 1;83(24). Epub 2017 Dec 1.

State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Microbial bioremediation is a promising approach for the removal of polycyclic aromatic hydrocarbon (PAH) contaminants. Many degraders of PAHs possess efflux pump genes in their genomes; however, their specific roles in the degradation of PAHs have not been clearly elucidated. In this study, two efflux pumps, TtgABC and SrpABC, were systematically investigated to determine their functions in a PAH-degrading strain B6-2 (DSM 28064). The disruption of genes or resulted in a defect in organic solvent tolerance. TtgABC was found to contribute to antibiotic resistance; SrpABC only contributed to antibiotic resistance under an artificial overproduced condition. Moreover, a mutant strain without did not maintain its activity in long-term biphenyl (BP) degradation, which correlated with the loss of cell viability. The expression of SrpABC was significantly upregulated in the course of BP degradation. BP, 2-hydroxybiphenyl, 3-hydroxybiphenyl, and 2,3-dihydroxybiphenyl (2,3-DHBP) were revealed to be the inducers of 2,3-DHBP was verified to be a substrate of pump SrpABC; SrpABC can enhance the tolerance to 2,3-DHBP by pumping it out. The mutant strain B6-2Δ prolonged BP degradation with the increase of expression. These results suggest that the pump SrpABC of strain B6-2 plays a positive role in BP biodegradation by pumping out metabolized toxic substances such as 2,3-DHBP. This study provides insights into the versatile physiological functions of the widely distributed efflux pumps in the biodegradation of PAHs. Polycyclic aromatic hydrocarbons (PAHs) are notorious for their recalcitrance to degradation in the environment. A high frequency of the occurrence of the efflux pump genes was observed in the genomes of effective PAH degraders; however, their specific roles in the degradation of PAHs are still obscure. The significance of our study is in the identification of the function and mechanism of the efflux pump SrpABC of strain B6-2 (DSM 28064) in the biphenyl degradation process. SrpABC is crucial for releasing the toxicity caused by intermediates that are unavoidably produced in PAH degradation, which enables an understanding of how cells maintain the intracellular balance of materials. The findings from this study provide a new perspective on PAH recalcitrance and shed light on enhancing PAH degradation by genetic engineering.
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http://dx.doi.org/10.1128/AEM.01882-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717210PMC
December 2017

Seasonality of active tuberculosis notification from 2005 to 2014 in Xinjiang, China.

PLoS One 2017 5;12(7):e0180226. Epub 2017 Jul 5.

Department of Respiratory Medicine, The First Teaching Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.

Objectives: Xinjiang is one of the highest TB-burdened provinces of China. A time-series analysis was conducted to evaluate the trend, seasonality of active TB in Xinjiang, and explore the underlying mechanism of TB seasonality by comparing the seasonal variations of different subgroups.

Methods: Monthly active TB cases from 2005 to 2014 in Xinjiang were analyzed by the X-12-ARIMA seasonal adjustment program. Seasonal amplitude (SA) was calculated and compared within the subgroups.

Results: A total of 277,300 confirmed active TB cases were notified from 2005 to 2014 in Xinjiang, China, with a monthly average of 2311±577. The seasonality of active TB notification was peaked in March and troughed in October, with a decreasing SA trend. The annual 77.31% SA indicated an annual mean of additional TB cases diagnosed in March as compared to October. The 0-14-year-old group had significantly higher SA than 15-44-year-old group (P<0.05). Students had the highest SA, followed by herder and migrant workers (P<0.05). The pleural TB cases had significantly higher SA than the pulmonary cases (P <0.05). Significant associations were not observed between SA and sex, ethnic group, regions, the result of sputum smear microcopy, and treatment history (P>0.05).

Conclusion: TB notification in Xinjiang shows an apparent seasonal variation with a peak in March and trough in October. For the underlying mechanism of TB seasonality, our results hypothesize that winter indoor crowding increases the risk of TB transmission, and seasonality was mainly influenced by the recent exogenous infection rather than the endogenous reactivation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180226PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497978PMC
September 2017

Socio-Demographic Predictors and Distribution of Pulmonary Tuberculosis (TB) in Xinjiang, China: A Spatial Analysis.

PLoS One 2015 7;10(12):e0144010. Epub 2015 Dec 7.

Department of Respiratory Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.

Objectives: Xinjiang is one of the high TB burden provinces of China. A spatial analysis was conducted using geographical information system (GIS) technology to improve the understanding of geographic variation of the pulmonary TB occurrence in Xinjiang, its predictors, and to search for targeted interventions.

Methods: Numbers of reported pulmonary TB cases were collected at county/district level from TB surveillance system database. Population data were extracted from Xinjiang Statistical Yearbook (2006~2014). Spatial autocorrelation (or dependency) was assessed using global Moran's I statistic. Anselin's local Moran's I and local Getis-Ord statistics were used to detect local spatial clusters. Ordinary least squares (OLS) regression, spatial lag model (SLM) and geographically-weighted regression (GWR) models were used to explore the socio-demographic predictors of pulmonary TB incidence from global and local perspectives. SPSS17.0, ArcGIS10.2.2, and GeoDA software were used for data analysis.

Results: Incidence of sputum smear positive (SS+) TB and new SS+TB showed a declining trend from 2005 to 2013. Pulmonary TB incidence showed a declining trend from 2005 to 2010 and a rising trend since 2011 mainly caused by the rising trend of sputum smear negative (SS-) TB incidence (p<0.0001). Spatial autocorrelation analysis showed the presence of positive spatial autocorrelation for pulmonary TB incidence, SS+TB incidence and SS-TB incidence from 2005 to 2013 (P <0.0001). The Anselin's Local Moran's I identified the "hotspots" which were consistently located in the southwest regions composed of 20 to 28 districts, and the "coldspots" which were consistently located in the north central regions consisting of 21 to 27 districts. Analysis with the Getis-Ord Gi* statistic expanded the scope of "hotspots" and "coldspots" with different intensity; 30 county/districts clustered as "hotspots", while 47 county/districts clustered as "coldspots". OLS regression model included the "proportion of minorities" and the "per capita GDP" as explanatory variables that explained 64% the variation in pulmonary TB incidence (adjR2 = 0.64). The SLM model improved the fit of the OLS model with a decrease in AIC value from 883 to 864, suggesting "proportion of minorities" to be the only statistically significant predictor. GWR model also improved the fitness of regression (adj R2 = 0.68, AIC = 871), which revealed that "proportion of minorities" was a strong predictor in the south central regions while "per capita GDP" was a strong predictor for the southwest regions.

Conclusion: The SS+TB incidence of Xinjiang had a decreasing trend during 2005-2013, but it still remained higher than the national average in China. Spatial analysis showed significant spatial autocorrelation in pulmonary TB incidence. Cluster analysis detected two clusters-the "hotspots", which were consistently located in the southwest regions, and the "coldspots", which were consistently located in the north central regions. The exploration of socio-demographic predictors identified the "proportion of minorities" and the "per capita GDP" as predictors and may help to guide TB control programs and targeting intervention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671667PMC
June 2016

Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems.

Biomater Sci 2016 Jan;4(1):104-14

Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

Considering the specific pH gradients of tumour microenvironments, a dual acid-responsive drug delivery system, which can respond to the tumor extracellular and intercellular pH stimuli, has been fabricated via simple host-guest recognition. Firstly, we synthesise 2,4,6-trimethoxybenzaldehyde modified dextran (Dex-TMBA) and mPEG-imine-β-cyclodextrin (PIC), respectively. And then, through the host-guest recognition between the cyclodextrin (CD) of PIC and the benzene ring of Dex-TMBA, a kind of dual acid-responsive supramolecular drug delivery system can be fabricated. Under neutral pH conditions, anticancer drugs can be loaded by forming supramolecular nanoparticles via the host-guest recognition. While, at tumor extracellular pH (∼6.8), the acid-labile benzoic-imine of PIC cleaves and the nanoparticles are amino positively charged to facilitate cell internalization. Subsequently, due to the hydrolysis of acetal bonds in Dex-TMBA under significantly increased acidity in subcellular compartments such as the endosomes (∼5.3), the loaded doxorubicin releases from the endocytosed drug delivery. This dual acid-responsive nanoparticles can efficiently load and release drugs, acting as drug delivery systems for enhancing anticancer efficiency.
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http://dx.doi.org/10.1039/c5bm00235dDOI Listing
January 2016

Hyperbranched PEG-based supramolecular nanoparticles for acid-responsive targeted drug delivery.

Biomater Sci 2015 Jun 13;3(6):870-8. Epub 2015 May 13.

Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China.

Herein, hyperbranched poly(ethylene glycol)-based supramolecular nanoparticles with pH-sensitive properties were designed and used for targeted drug delivery. Via host-guest recognition between benzimidazole anchored poly(ethylene glycol)-hyperbranched polyglycerol (PEG-HPG-BM) and folic acid modified CD (FA-CD), targeted supramolecular nanoparticles (TSNs) were fabricated. At neutral aqueous conditions TSNs could load the model drug DOX. While under intracellular acidic conditions the loaded-drug would be released due to the protonation of BM. This protonation allowed the supramolecular nanoparticles to expand or even disassemble, which showes the pH-dependent property. The introduction of the active targeting FA molecule and the specific interactions with the receptor of HeLa cells means that DOX-loaded TSNs show a significantly improved anticancer efficacy. In vitro drug release assays and intracellular experiments confirmed that TSNs had an obvious pH-sensitive property and remarkably improved anticancer effects, which hold great potential for further biomedical applications such as anticancer drug delivery.
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http://dx.doi.org/10.1039/c5bm00061kDOI Listing
June 2015

pH-responsive metallo-supramolecular nanogel for synergistic chemo-photodynamic therapy.

Acta Biomater 2015 Oct 16;25:162-71. Epub 2015 Jul 16.

Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

Unlabelled: Benefited from the high orientation of coordinated interaction, metallo-supramolecular materials have attracted enormous interest in many fields. Herein, a novel metallo-supramolecular nanogel (SNG)-based drug delivery system for synergistic chemo-photodynamic therapy is explored to enhance anticancer efficacy. It is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. It can respond to tumor acid microenvironment to release the co-delivered anticancer drug and photosensitizer to kill the lesion cells. Zn-Por moieties in SNG keep the photosensitivity in the range of visible wavelength and possess the ability of generating active oxygen species for photodynamic therapy. The drug-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy. Compared with the single chemotherapy of free doxorubicine (DOX) or photodynamic therapy of Zn-Por in SNG, DOX-loaded SNG with irradiation shows higher in vitro cytotoxicity and in vivo anticancer therapeutic activity, endowing the SNG with great potential in cancer treatments.

The Statement Of Significance: A combination of multiple non-cross-resistant anticancer agents has been widely applied clinically. Applying multiple drugs with different molecular targets can raise the genetic barriers and delay the cancer adaption process. Multiple drugs targeting different cellular pathways can function synergistically, giving higher therapeutic efficacy and target selectivity. Overall, developing a combination therapeutic approach might even be the key to enhance anticancer efficacy and overcome chemo-resistance. Herein, a novel metallo-supramolecular nanogel (SNG) is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. The DOX-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy because it can respond to tumor acid microenvironment to release the co-delivered anticancer drug and photosensitizer to kill the lesion cells.
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http://dx.doi.org/10.1016/j.actbio.2015.07.024DOI Listing
October 2015

Acid-Sensitive Nanogels for Synergistic Chemo-Photodynamic Therapy.

Macromol Biosci 2015 Nov 14;15(11):1563-70. Epub 2015 Jul 14.

Department of Chemistry, Northeast Normal University, Changchun, 130024, P. R. China.

Herein, a novel kind of intelligent nanogels have been designed, which can spatiotemporally control the release of drug (doxorubicin) and photosensitizers (porphyrins) to combine chemo-therapy and photodynamic therapy. Further, the fluorescing properties of porphyrins make it possible to be used as a kind of diagnostic bio-imaging agents. In vitro release assays confirm that DOX-loaded nanogels show obvious intracellular pH-sensitive property. The intracellular experiments further prove that drug-loaded nanogels has the significantly antitumor efficacy due to the combination of chemotherapy and photodynamic therapy, which made this drug delivery system hold great potential applications for further cancer treatment.
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http://dx.doi.org/10.1002/mabi.201500180DOI Listing
November 2015

Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer.

Mol Med Rep 2015 Oct 3;12(4):5246-54. Epub 2015 Jul 3.

Department of Pathology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.

The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)‑mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E‑binding protein 1 (4E‑BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p‑mTOR, p‑4E‑BP1, p‑S6K1, and the clinicopathological parameters of breast cancer were also determined. p‑mTOR, p‑4E‑BP1 and p‑S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease‑free survival rate was examined using survival analyses and Log‑rank tests. The results of the present study indicated that the expression levels of p‑mTOR, p‑4E‑BP1, and p‑S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (P<0.01). p‑mTOR was predominantly expressed in the cytoplasm, whereas p‑4E‑BP1 and p‑S6K1 were predominantly co‑expressed in the cytoplasm and the nucleus. In addition, p‑4E‑BP1 and p‑S6K1 were more likely to be expressed in the cytoplasm in breast cancer tissue samples, as compared with normal tissue samples (P<0.001). Positive p‑mTOR was not significantly correlated with positive p‑4E‑BP1 and p‑S6K1 expression. The survival analyses of the patients with positive p‑mTOR, p‑4E‑BP1, and p‑S6K1 tissue samples were not significantly different from those of the patients with negative tissue samples (P>0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p‑mTOR, p‑4E‑BP1, and p‑S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p‑4E‑BP1 and p‑S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p‑mTOR, p‑4E‑BP1, and p‑S6K1 are not prognostic factors for breast cancer.
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http://dx.doi.org/10.3892/mmr.2015.4037DOI Listing
October 2015

Dual pH-responsive mesoporous silica nanoparticles for efficient combination of chemotherapy and photodynamic therapy.

J Mater Chem B 2015 Jun 26;3(23):4707-4714. Epub 2015 May 26.

Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China.

A kind of dual pH-responsive mesoporous silica nanoparticle (MSN)-based drug delivery system, which can respond to the cancer extracellular and intercellular pH stimuli, has been fabricated for synergistic chemo-photodynamic therapy. By grafting histidine onto the silica surface, the acid sensitive PEGylated tetraphenylporphyrin zinc (Zn-Por-CA-PEG) can be used as a gatekeeper to block the nanopores of MSNs by the metallo-supramolecular-coordinated interaction between Zn-Por and histidine. This gatekeeper is stable enough to prevent the loaded drug from leaching out in healthy tissue. However, at cancer extracellular pH (∼6.8) the conjugated acid sensitive cis-aconitic anhydride (CA) between Zn-Por and PEG will cleave and the surface of Zn-Por will be amino positively charged to facilitate cell internalization. Furthermore, the metallo-supramolecular-coordination will disassemble in intracellular acidic microenvironments (∼5.3) to release the carried drug and Zn-Por due to the removal of the gatekeeper. The photosensitivity of Zn-Por further makes it possible to combine chemotherapy and photodynamic therapy. This dual pH-sensitive MSN-based drug delivery system showed higher in vitro cytotoxicity than the single chemotherapy of free DOX or photodynamic therapy of Zn-Por, presenting its great potential for cancer treatment to overcome the challenges in efficient delivery in the site and ideal anti-cancer efficacy.
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http://dx.doi.org/10.1039/c5tb00256gDOI Listing
June 2015

Fabrication of modular multifunctional delivery for antitumor drugs based on host-guest recognition.

Acta Biomater 2015 May 5;18:168-75. Epub 2015 Mar 5.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address:

Herein, learning from the idea of the modular concept widely used in ship building, as a design approach that assembles some subdivided smaller modules to a specific ship, a new modular multifunctional drug delivery (MMDD) with excellent biocompatibility was directly prepared by a flexible host-guest interaction between pH-sensitive benzimidazole-graft-dextran (Dex-BM) and pre-synthesized multifunctional cyclodextrins. In this drug system, pH-sensitive Dex-BM acted as the main case and pre-synthesized multifunctional cyclodextrins were the changeable modules. To verify the feasibility of MMDD in cancer chemotherapy, doxorubicin (DOX) was used as a model drug. In vitro drug release experiments indicated that the drug released around 80% from DOX-loaded MMDD at pH 5.3, while approximately 40% of DOX released under the condition of pH 7.4. Moreover, the targeting antitumor activity of DOX-loaded MMDD was investigated in HeLa and HepG2 cells using MTT assays, confocal laser scanning microscopy and flow cytometer, which indicated that the targeted DOX-loaded MMDD provided an efficient drug delivery platform for inhibition of different cancer cells. Meantime, the incorporation of different functional modules into one system was also investigated, simultaneously exhibiting targeting and imaging property. These features suggest that this modular multifunctional drug delivery system can efficiently enhance the inhibition of cellular proliferation in vitro, and according to the needs in clinical treatment, some targeting and imaging molecules can be chosen.
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http://dx.doi.org/10.1016/j.actbio.2015.02.029DOI Listing
May 2015

A retrospective study of the clinical differences of Uygur breast cancer patients compared to Han breast cancer patients in the Xinjiang region of China.

Int J Clin Exp Med 2014 15;7(10):3482-90. Epub 2014 Oct 15.

Department of Breast and Neck, The Affiliated Tumor Hospital of Xinjiang Medical University 789 East Suzhou Street, Urumqi 830011, Xinjiang, China.

Background: Studies support biological disparities of breast cancer among races/ethnicities. Uygur is a minority ethnic group in China with a genetic admixture of Caucasian and East Asian. The Han ethnic group makes up the majority of the Chinese population. We aim to study and compare the clinical differences and survival rate in these two ethnic groups in order to improve prophylaxis.

Methods: A retrospective analysis of the medical records of 264 Uygur and 287 Han breast cancer patients including demographic data, clinical and pathological parameters, TNM status, Ki-67 and treatment information was collected. The patients were followed up at three month intervals for 2 years then every 6 months for 3 to 4 years postoperatively. Chi-square tests were performed to compare characteristics, and a log-rank test was used for ranked data. Overall survival and disease free survival were analyzed by Kaplan Meier tests.

Results: Uygur was statistically different in terms of: marital status; occupation; body mass index; duration of breast feeding; period of complaint; pathological composition; size of primary tumor; number of metastatic and resected lymph nodes; pathological staging; expression of nm23; chemotherapy and radiotherapy. The 5-year overall survival rate of Uygur breast cancer patients was 89.2% compared to 91.7% in Han (P = 0.129). The disease free survival of Uygur breast cancer patients was 79.3% compared to 84.5% in Han (P = 0.040).

Conclusion: The different characteristics of Uygur breast cancer patients compared to Han breast cancer patients and their lower survival rates indicate that management strategies should be implemented to improve patient outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238510PMC
November 2014

Metallo-supramolecular nanogels for intracellular pH-responsive drug release.

Macromol Rapid Commun 2014 Oct 1;35(19):1697-705. Epub 2014 Sep 1.

Department of Chemistry, Northeast Normal University, Changchun, 130024, China.

A simple process is developed to fabricate metallo-supramolecular nanogels (MSNs) by the metallo-supramolecular-coordinated interaction between histidine and iron-meso-tetraphenylporphin. MSNs are composed of histidine-modified dextran (DH) and iron-meso-tetraphenylporphin (Fe-Por) and exhibit excellent biocompatibility and stability. MSNs show pH responsiveness in the intracellular mildly acidic environment, which has great potential for acid-triggered drug release delivery. In vitro drug release profiles demonstrate that the pH-dependent disassembly of MSNs to histidine and Por results in a quicker release rate of loaded-DOX at pH 5.3, while at pH 7.4 MSNs could hinder the release of loaded-DOX due to the enhanced stability of MSNs.
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http://dx.doi.org/10.1002/marc.201400291DOI Listing
October 2014

Boronic acid shell-crosslinked dextran-b-PLA micelles for acid-responsive drug delivery.

Macromol Biosci 2014 Nov 21;14(11):1609-18. Epub 2014 Aug 21.

Department of Chemistry, Northeast Normal University, Changchun, 130024, P. R. China.

Herein, 3-carboxy-5-nitrophenylboronic acid (CNPBA) shell-crosslinked micelles based on amphiphilic dextran-block-polylactide (Dex-b-PLA) are prepared and used for efficient intracellular drug deliveries. Due to the reversible pH-dependent binding with diols to form boronate esters, CNPBA modified Dex-b-PLA shows excellent pH-sensitivity. In neutral aqueous conditions, CNPBA-Dex-b-PLA forms shell-crosslinked micelles to enable DOX loading, while in acid conditions, the boronate esters hydrolyze and the micelles de-crosslink to release loaded DOX. In vitro release studies indicate that the release of the DOX cargo is minimized at physiological conditions, while there is a burst release in response to low pHs. The cell viability of CNPBA-Dex-b-PLA investigated by MTT assay was more than 90%, indicating that, as a drug delivery system, CNPBA-Dex-b-PLA has good cytocompatibility. These features suggest that the pH-responsive biodegradable CNPBA-Dex-b-PLA can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform as a drug delivery system for cancer therapy.
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http://dx.doi.org/10.1002/mabi.201400251DOI Listing
November 2014

Intercellular pH-responsive histidine modified dextran-g-cholesterol micelle for anticancer drug delivery.

Colloids Surf B Biointerfaces 2014 Sep 28;121:36-43. Epub 2014 May 28.

Changchun Institutes of Applied Chemistry, Changchun 130022, PR China.

Herein, the micelles based on histidine modified dextran-g-cholesterol (HDC) were successfully prepared which exhibited excellent pH-responsive behavior in acidic aqueous solution (pH<6, within the range of malignant cellular endosome). Taking advantage of this pH-sensitivity in acidic conditions, doxorubicin (DOX), a model anticancer drug, was effectively loaded into the micelles via hydrophobic interactions. The DOX release from all DOX-loaded micelles was accelerated in acid conditions mimicking the endosomal/lysosomal compartments. The enhanced intracellular DOX release was also observed in MCF-7 cells. DOX-loaded pH-sensitive micelles showed higher cellular proliferation inhibition toward MCF-7 cells than that of pH-insensitive micelles. These features suggested that the micelles could efficiently load and deliver DOX into tumor cells, which can enhance the inhibition of cellular proliferation in vitro, providing a powerful mean for delivering and releasing cargoes at the tumor sites.
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http://dx.doi.org/10.1016/j.colsurfb.2014.05.032DOI Listing
September 2014

Intracellular pH-sensitive metallo-supramolecular nanogels for anticancer drug delivery.

ACS Appl Mater Interfaces 2014 May 1;6(10):7816-22. Epub 2014 May 1.

Department of Chemistry, Northeast Normal University , Changchun 130024, P. R. China.

For drug delivery systems, the most important factors are biocompatibility and stability. To achieve excellent biocompatibility, learning from naturally occurring systems may be the best choice. Herein, a series of pH-sensitive metallo-supramolecular nanogels (MSNs) were prepared by the metallo-supramolecular coordinated interaction between histidine and iron-meso-tetraphenylporphin, which mimicks the way that hemoglobin carries oxygen. With the excellent biocompatibility and special supramolecular pH sensitivity, MSNs had been exploited to load and release anticancer drug doxorubicin (DOX). In vitro drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while up to about 80% of the loaded DOX could be quickly released at pH 5.3 due to the pH-dependent disassembly of MSNs. Confocal laser scanning microscopy (CLSM) and flow cytometry were used to verify the cellular uptake and intracellular drug release behaviors of DOX-loaded MSNs toward MCF-7. Efficient cellular proliferation inhibition against MCF-7 and HeLa cells was also observed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. These features suggested that MSNs could be of great potential as intelligent drug delivery systems.
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http://dx.doi.org/10.1021/am501093aDOI Listing
May 2014

Dual responsive supramolecular nanogels for intracellular drug delivery.

Chem Commun (Camb) 2014 Apr 12;50(29):3789-91. Epub 2014 Feb 12.

Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China.

Supramolecular nanogels cross-linked by host-guest interaction between dextran grafted benzimidazole (Dex-g-BM) and thiol-β-cyclodextrin were designed. Their special supramolecular pH-sensitivity under acidic conditions (pH < 6, within the range of malignant cellular endosomes) and reduction sensitivity in response to biologically relevant stimuli will be of great advantage to the future of cancer chemotherapeutics.
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http://dx.doi.org/10.1039/c4cc00016aDOI Listing
April 2014

The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

PLoS One 2014 23;9(1):e85905. Epub 2014 Jan 23.

Care Division, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Background And Objective: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury.

Methods And Design: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays.

Results: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes.

Conclusions: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085905PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900431PMC
November 2014

A Dicer-1 gene from white shrimp Litopenaeus vannamei: expression pattern in the processes of immune response and larval development.

Fish Shellfish Immunol 2010 Oct 25;29(4):565-70. Epub 2010 Jun 25.

Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.

Dicer is a member of the RNAase III family which catalyzes the cleavage of double-stranded RNA to small interfering RNAs and micro RNAs, and then directs sequence-specific gene silencing. In this paper, the full-length cDNA of Dicer-1 was cloned from white shrimp Litopenaeus vannamei (designated as LvDcr1). It was of 7636 bp, including a poly A tail, a 5' UTR of 136 bp, a 3' UTR of 78 bp, and an open reading frame (ORF) of 7422 bp encoding a putative protein of 2473 amino acids. The predicted amino acid sequence comprised all recognized functional domains found in other Dicer-1 homologues and showed the highest (97.7%) similarity to the Dicer-1 from tiger shrimp Penaeus mondon. Quantitative real-time PCR was employed to investigate the tissue distribution of LvDcr1 mRNA, and its expression in shrimps under virus challenge and larvae at different developmental stages. The LvDcr1 mRNA could be detected in all examined tissues with the highest expression level in hemocyte, and was up-regulated in hemocytes and gills after virus injection. These results indicated that LvDcr1 was involved in antiviral defense in adult shrimp. During the developmental stages from fertilized egg to postlarva VII, LvDcr1 was constitutively expressed at all examined development stages, but the expression level varied significantly. The highest expression level was observed in fertilized eggs and followed a decrease from fertilized egg to nauplius I stage. Then, the higher levels of expression were detected at nauplius V and postlarva stages. LvDcr1 expression regularly increased at the upper phase of nauplius, zoea and mysis stages than their prophase. The different expression of LvDcr1 in the larval stages could provide clues for understanding the early innate immunity in the process of shrimp larval development.
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http://dx.doi.org/10.1016/j.fsi.2010.05.016DOI Listing
October 2010
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