Summer and winter campaigns for the chemical compositions and sources of nonmethane hydrocarbons(NMHCs)and oxygenated volatile organic compounds(OVOCs)were conducted in Xi’an.Data from 57 photochemical assessment mon...Summer and winter campaigns for the chemical compositions and sources of nonmethane hydrocarbons(NMHCs)and oxygenated volatile organic compounds(OVOCs)were conducted in Xi’an.Data from 57 photochemical assessment monitoring stations for NMHCs and 20 OVOC species were analyzed.Significant seasonal differences were noted for total VOC(TVOC,NMHCs and OVOCs)concentrations and compositions.The campaign-average TVOC concentrations in winter(85.3±60.6 ppbv)were almost twice those in summer(47.2±31.6 ppbv).Alkanes and OVOCs were the most abundant category in winter and summer,respectively.NMHCs,but not OVOCs,had significantly higher levels on weekends than on weekdays.Total ozone formation potential was higher in summer than in winter(by 50%)because of the high concentrations of alkenes(particularly isoprene),high temperature,and high solar radiation levels in summer.The Hybrid Environmental Receptor Model(HERM)was used to conduct source apportionment for atmospheric TVOCs in winter and summer,with excellent accuracy.HERM demonstrated its suitability in a situation where only partial source profile data were available.The HERM results indicated significantly different seasonal source contributions to TVOCs in Xi’an.In particular,coal and biomass burning had contributions greater than half in winter(53.4%),whereas traffic sources were prevalent in summer(53.1%).This study’s results highlight the need for targeted and adjustable VOC control measures that account for seasonal differences in Xi’an;such measures should target not only the severe problem with VOC pollution but also the problem of consequent secondary pollution(e.g.,from ozone and secondary organic aerosols).展开更多
The constrained weighted-non-negative matrix factorization(CW-NMF)hybrid receptor model was applied to study the influence of steelmaking activities on PM_(2.5)(particulate matter with equivalent aerodynamic diameter ...The constrained weighted-non-negative matrix factorization(CW-NMF)hybrid receptor model was applied to study the influence of steelmaking activities on PM_(2.5)(particulate matter with equivalent aerodynamic diameter less than 2.5μm)composition in Dunkerque,Northern France.Semi-diurnal PM_(2.5)samples were collected using a high volume sampler in winter 2010 and spring 2011 and were analyzed for trace metals,water-soluble ions,and total carbon using inductively coupled plasma–atomic emission spectrometry(ICP-AES),ICP-mass spectrometry(ICP-MS),ionic chromatography and micro elemental carbon analyzer.The elemental composition shows that NO_(3)^(-),SO_(4)^(2-),NH_4~+and total carbon are the main PM_(2.5)constituents.Trace metals data were interpreted using concentration roses and both influences of integrated steelworks and electric steel plant were evidenced.The distinction between the two sources is made possible by the use Zn/Fe and Zn/Mn diagnostic ratios.Moreover Rb/Cr,Pb/Cr and Cu/Cd combination ratio are proposed to distinguish the ISW-sintering stack from the ISW-fugitive emissions.The a priori knowledge on the influencing source was introduced in the CW-NMF to guide the calculation.Eleven source profiles with various contributions were identified:8 are characteristics of coastal urban background site profiles and 3 are related to the steelmaking activities.Between them,secondary nitrates,secondary sulfates and combustion profiles give the highest contributions and account for 93%of the PM_(2.5)concentration.The steelwork facilities contribute in about 2%of the total PM_(2.5)concentration and appear to be the main source of Cr,Cu,Fe,Mn,Zn.展开更多
In this work, receptor models were used to identify the PM2.5 sources and its contribution to the air quality in residential, comercial and industrial sampling sites in the Metropolitan Area of Costa Rica. Principal c...In this work, receptor models were used to identify the PM2.5 sources and its contribution to the air quality in residential, comercial and industrial sampling sites in the Metropolitan Area of Costa Rica. Principal component analysis with absolute principal component scores (PCA-APCS), UNIMX and positive matrix factorization (PMF) was applied to analyze the data collected during 1 year of sampling campaign (2010-2011). The PM2.5 samples were characterized through its composition looking for trace elements, inorganic ions and organic and elemental carbon. These three models identified some common sources of PM2.5: marine aerosol, crustal material, traffic, secondary aerosols (secondary sulfate and secondary nitrate resolved by PMF), a mixed source of heavy fuels combustion and biomass burning, and industrial emissions. The three models predicted that the major sources of PM2.5 in the Metropolitan Area of Costa Rica were related to anthropogenic sources (73%, 65% and 69%, respectively, for PCA-APCS, Unmix and PMF) although natural sources also contributed to PM2.5 (21%, 24% and 26%). On average, PCA and PMF methods resolved 94% and 95% of the PM2.5 mass concentrations, respectively. The results were comparable to the estimate using UNMIX.展开更多
Receptor models are a useful tool for identifying sources of polycyclic aromatic hydrocarbons(PAHs)in multiple environmental media.In this study,three different receptor models(including the principal component analys...Receptor models are a useful tool for identifying sources of polycyclic aromatic hydrocarbons(PAHs)in multiple environmental media.In this study,three different receptor models(including the principal component analysis-multiple linear regression(PCA-MLR),positive matrix factorization(PMF),and Unmix models)were used to apportion the sources of 16 priority PAHs in a sediment core of Lake Dagze Co.TheΣPAHs(sum of all 16 measured PAHs)concentrations ranged from 51.89 to 132.82 ng/g with an average of 80.39 ng/g.TheΣPAHs were dominated by 2-3 ring PAHs,accounting for 80.12%on average,thereby indicating that they mainly originated from biomass and coal combustion and/or from long-range atmospheric transportation.The three models produced consistent source apportionment results.The greatest contributor toΣPAHs was biomass combustion,followed by coal combustion,vehicle emissions,and petrogenic sources.Moreover,the temporal variation of the common sources was well-correlated among models.The multi-method comparison and evaluation results showed that all three models were useful tools for source apportionment of PAHs,with the PMF model providing better results than the PCA-MLR and Unmix models.The temporal trends of factor contributions were verified by PAHs with different ring numbers.Significant correlations were found between the simulated concentrations of each source factor and the PAHs with different ring numbers(P<0.01),except for the petrogenic source identified by the Unmix model(P>0.05).This study can provide useful information for further investigation of source apportionment of PAHs in the sediment cores.展开更多
The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse mod...The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.展开更多
Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacter...Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacterium） on the expression of TLR4 and tumor necrosis factor-alpha （TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid （TNBS）/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group （P〈0.01 for both）. No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group （P〉0.05）, whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group （P〈0.01）. There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.展开更多
Addiction to nicotine, and possibly other tobacco constituents, is a major factor that contributes to the difficulties smokers face when attempting to quit smoking. Amongst the various subtypes of nicotinic acetylchol...Addiction to nicotine, and possibly other tobacco constituents, is a major factor that contributes to the difficulties smokers face when attempting to quit smoking. Amongst the various subtypes of nicotinic acetylcholine receptors (nAChRs), the α4β2 subtype plays an important role in mediating the addiction process. The characterization of human α4β2-ligand binding interactions provides a molecular framework for understanding ligand-receptor interactions, rendering insights into mechanisms of nicotine addiction and may furnish a tool for efficiently identifying ligands that can bind the nicotine receptor. Therefore, we constructed a homology model of human α4β2 nAChR and performed molecular docking and molecular dynamics (MD) simulations to elucidate the potential human α4β2-ligand binding modes for eleven compounds known to bind to this receptor. Residues V96, L97 and F151 of the α4 subunit and L111, F119 and F121 of the β2 subunit were found to be involved in hydrophobic interactions while residues S153 and W154 of the α4 subunit were involved in the formation of hydrogen bonds between the receptor and respective ligands. The homology model and its eleven ligand-bound structures will be used to develop a virtual screening program for identifying tobacco constituents that are potentially addictive.展开更多
Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of I...Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.展开更多
Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications...Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.展开更多
Interleukin-10 (IL-10) is an important cytokine that plays a pivotal role in natural and adaptive immune systems. However, in lower vertebrates, especially in teleost the receptor of this cytokine is still largely unk...Interleukin-10 (IL-10) is an important cytokine that plays a pivotal role in natural and adaptive immune systems. However, in lower vertebrates, especially in teleost the receptor of this cytokine is still largely unknown. This paper described the cloning and characterization of grass carp interleukin-10 receptor 1 (gcIL10R1) and the 3D structure of its extracellular domain was predicted. The gcIL10R1 cDNA included 180 bp5’ untranslated region (UTR), 870 bp3’ UTR and an open reading frame (ORF) of 1632 bp. The ORF was found to encode a 543 amino acid protein with a putative JAK1 binding site, one STAT3 binding site. The phylogenetic analysis clusters gcIL10R1 with other teleost IL10R1s but independently of the amphibian, avian and mammalian IL10R1s. The 3D structure of its extracellular domain was the first homology model of a fish IL10R1 that revealed a high similarity with its mammalian and avian counterparts.展开更多
Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i....Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i.e., bioactive com- pounds obtained from Ecteinascidia turbinate to treat some types of cancer or rapamycin from Streptomyces hygroscop- icus to prevent organ rejection after transplant. This trend will continue simply due to the fact that Mother Nature has been synthesizing molecules for millions of years. In our lab- oratory, we have characterized several compounds obtained from natural sources and that possess important neuronal effects,展开更多
N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning m...N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.展开更多
基金This research was supported by the Natural Science Foundation of China(Grant No.41907188)Natural Science Foundation of Shaanxi Province,China(Grant No.2019JQ-386)the China Postdoctoral Science Foundation(Grant No.2019M653658).
文摘Summer and winter campaigns for the chemical compositions and sources of nonmethane hydrocarbons(NMHCs)and oxygenated volatile organic compounds(OVOCs)were conducted in Xi’an.Data from 57 photochemical assessment monitoring stations for NMHCs and 20 OVOC species were analyzed.Significant seasonal differences were noted for total VOC(TVOC,NMHCs and OVOCs)concentrations and compositions.The campaign-average TVOC concentrations in winter(85.3±60.6 ppbv)were almost twice those in summer(47.2±31.6 ppbv).Alkanes and OVOCs were the most abundant category in winter and summer,respectively.NMHCs,but not OVOCs,had significantly higher levels on weekends than on weekdays.Total ozone formation potential was higher in summer than in winter(by 50%)because of the high concentrations of alkenes(particularly isoprene),high temperature,and high solar radiation levels in summer.The Hybrid Environmental Receptor Model(HERM)was used to conduct source apportionment for atmospheric TVOCs in winter and summer,with excellent accuracy.HERM demonstrated its suitability in a situation where only partial source profile data were available.The HERM results indicated significantly different seasonal source contributions to TVOCs in Xi’an.In particular,coal and biomass burning had contributions greater than half in winter(53.4%),whereas traffic sources were prevalent in summer(53.1%).This study’s results highlight the need for targeted and adjustable VOC control measures that account for seasonal differences in Xi’an;such measures should target not only the severe problem with VOC pollution but also the problem of consequent secondary pollution(e.g.,from ozone and secondary organic aerosols).
基金financially supported by the Nord-Pas-de-Calais Region Councilthe Ministry of Higher Education and Research+1 种基金the European Regional Development FundsAdib Kfoury acknowledges the“Pole Metropolitain Cote d'Opale”(PMCO)for its PhD financial support
文摘The constrained weighted-non-negative matrix factorization(CW-NMF)hybrid receptor model was applied to study the influence of steelmaking activities on PM_(2.5)(particulate matter with equivalent aerodynamic diameter less than 2.5μm)composition in Dunkerque,Northern France.Semi-diurnal PM_(2.5)samples were collected using a high volume sampler in winter 2010 and spring 2011 and were analyzed for trace metals,water-soluble ions,and total carbon using inductively coupled plasma–atomic emission spectrometry(ICP-AES),ICP-mass spectrometry(ICP-MS),ionic chromatography and micro elemental carbon analyzer.The elemental composition shows that NO_(3)^(-),SO_(4)^(2-),NH_4~+and total carbon are the main PM_(2.5)constituents.Trace metals data were interpreted using concentration roses and both influences of integrated steelworks and electric steel plant were evidenced.The distinction between the two sources is made possible by the use Zn/Fe and Zn/Mn diagnostic ratios.Moreover Rb/Cr,Pb/Cr and Cu/Cd combination ratio are proposed to distinguish the ISW-sintering stack from the ISW-fugitive emissions.The a priori knowledge on the influencing source was introduced in the CW-NMF to guide the calculation.Eleven source profiles with various contributions were identified:8 are characteristics of coastal urban background site profiles and 3 are related to the steelmaking activities.Between them,secondary nitrates,secondary sulfates and combustion profiles give the highest contributions and account for 93%of the PM_(2.5)concentration.The steelwork facilities contribute in about 2%of the total PM_(2.5)concentration and appear to be the main source of Cr,Cu,Fe,Mn,Zn.
文摘In this work, receptor models were used to identify the PM2.5 sources and its contribution to the air quality in residential, comercial and industrial sampling sites in the Metropolitan Area of Costa Rica. Principal component analysis with absolute principal component scores (PCA-APCS), UNIMX and positive matrix factorization (PMF) was applied to analyze the data collected during 1 year of sampling campaign (2010-2011). The PM2.5 samples were characterized through its composition looking for trace elements, inorganic ions and organic and elemental carbon. These three models identified some common sources of PM2.5: marine aerosol, crustal material, traffic, secondary aerosols (secondary sulfate and secondary nitrate resolved by PMF), a mixed source of heavy fuels combustion and biomass burning, and industrial emissions. The three models predicted that the major sources of PM2.5 in the Metropolitan Area of Costa Rica were related to anthropogenic sources (73%, 65% and 69%, respectively, for PCA-APCS, Unmix and PMF) although natural sources also contributed to PM2.5 (21%, 24% and 26%). On average, PCA and PMF methods resolved 94% and 95% of the PM2.5 mass concentrations, respectively. The results were comparable to the estimate using UNMIX.
基金supported by the National Natural Science Foundation of China(Nos.41773097,41971286)the Postgraduate Research Innovation project of Jiangsu Province(No.KYCX21_1330)。
文摘Receptor models are a useful tool for identifying sources of polycyclic aromatic hydrocarbons(PAHs)in multiple environmental media.In this study,three different receptor models(including the principal component analysis-multiple linear regression(PCA-MLR),positive matrix factorization(PMF),and Unmix models)were used to apportion the sources of 16 priority PAHs in a sediment core of Lake Dagze Co.TheΣPAHs(sum of all 16 measured PAHs)concentrations ranged from 51.89 to 132.82 ng/g with an average of 80.39 ng/g.TheΣPAHs were dominated by 2-3 ring PAHs,accounting for 80.12%on average,thereby indicating that they mainly originated from biomass and coal combustion and/or from long-range atmospheric transportation.The three models produced consistent source apportionment results.The greatest contributor toΣPAHs was biomass combustion,followed by coal combustion,vehicle emissions,and petrogenic sources.Moreover,the temporal variation of the common sources was well-correlated among models.The multi-method comparison and evaluation results showed that all three models were useful tools for source apportionment of PAHs,with the PMF model providing better results than the PCA-MLR and Unmix models.The temporal trends of factor contributions were verified by PAHs with different ring numbers.Significant correlations were found between the simulated concentrations of each source factor and the PAHs with different ring numbers(P<0.01),except for the petrogenic source identified by the Unmix model(P>0.05).This study can provide useful information for further investigation of source apportionment of PAHs in the sediment cores.
文摘The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.
基金supported the grants from the Natural Science Foundation of Hubei province(No.2012FFB02325)the National Natural Science Foundation of China(No.81000159)
文摘Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacterium） on the expression of TLR4 and tumor necrosis factor-alpha （TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid （TNBS）/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group （P〈0.01 for both）. No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group （P〉0.05）, whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group （P〈0.01）. There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.
文摘Addiction to nicotine, and possibly other tobacco constituents, is a major factor that contributes to the difficulties smokers face when attempting to quit smoking. Amongst the various subtypes of nicotinic acetylcholine receptors (nAChRs), the α4β2 subtype plays an important role in mediating the addiction process. The characterization of human α4β2-ligand binding interactions provides a molecular framework for understanding ligand-receptor interactions, rendering insights into mechanisms of nicotine addiction and may furnish a tool for efficiently identifying ligands that can bind the nicotine receptor. Therefore, we constructed a homology model of human α4β2 nAChR and performed molecular docking and molecular dynamics (MD) simulations to elucidate the potential human α4β2-ligand binding modes for eleven compounds known to bind to this receptor. Residues V96, L97 and F151 of the α4 subunit and L111, F119 and F121 of the β2 subunit were found to be involved in hydrophobic interactions while residues S153 and W154 of the α4 subunit were involved in the formation of hydrogen bonds between the receptor and respective ligands. The homology model and its eleven ligand-bound structures will be used to develop a virtual screening program for identifying tobacco constituents that are potentially addictive.
基金supported by funding from Innovative Research Team in Nanjing Medical University(IRT0631)the collaborating Grants(30611120524)
文摘Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.
基金supported by NIAMS,of the National Institutes of Health,under award numbers R01AR062074 (to DJD) and R01AR060636 (to S-JL)the Harry Headley Charitable and Research Foundation,Punta Gorda,FL(to ELG-L)
文摘Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.
文摘Interleukin-10 (IL-10) is an important cytokine that plays a pivotal role in natural and adaptive immune systems. However, in lower vertebrates, especially in teleost the receptor of this cytokine is still largely unknown. This paper described the cloning and characterization of grass carp interleukin-10 receptor 1 (gcIL10R1) and the 3D structure of its extracellular domain was predicted. The gcIL10R1 cDNA included 180 bp5’ untranslated region (UTR), 870 bp3’ UTR and an open reading frame (ORF) of 1632 bp. The ORF was found to encode a 543 amino acid protein with a putative JAK1 binding site, one STAT3 binding site. The phylogenetic analysis clusters gcIL10R1 with other teleost IL10R1s but independently of the amphibian, avian and mammalian IL10R1s. The 3D structure of its extracellular domain was the first homology model of a fish IL10R1 that revealed a high similarity with its mammalian and avian counterparts.
文摘Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i.e., bioactive com- pounds obtained from Ecteinascidia turbinate to treat some types of cancer or rapamycin from Streptomyces hygroscop- icus to prevent organ rejection after transplant. This trend will continue simply due to the fact that Mother Nature has been synthesizing molecules for millions of years. In our lab- oratory, we have characterized several compounds obtained from natural sources and that possess important neuronal effects,
文摘N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.
