Ion diffusion kinetics,depending on the size,tortuosity,connectivity of the channels,greatly affects the rate performance of the electrodes.Two-dimensional materials(2DMs) has emerged as promising electrode materials ...Ion diffusion kinetics,depending on the size,tortuosity,connectivity of the channels,greatly affects the rate performance of the electrodes.Two-dimensional materials(2DMs) has emerged as promising electrode materials in the past decades.Howeve r,the applications of 2DMs electrodes are limited by the strong restacking problem,which leads to a poor rate capability.In this work,we for the first time mediated the mo rphology of molybdenum disulfide(MoS_(2)) nanosheets via a facile coagulation method;abundant sheet crumples were induced,which greatly enhance their surface accessibility and thus benefit the ion diffusion kinetics.Consequently,the crumpled-MoS_(2) electrodes follow a capacitive Na-ion charge-storage mechanism to a large extent.Importantly,we demonstrate the special role of organic cations in the inter-sheet assembly configuration,in sharp contrast with that of alkali/alkaline-earth ones.We propose that organic cations cause edge/face contact of the sheets,instead of the face/face contact,thus affording a house-of-cards structure.展开更多
Here in this paper, we demonstrate a facile technique for creating the mixed formamidinium(HN = CHNH_3~+, FA~+)and methylammonium(CH_3NH_3~+, MA~+) cations in the lead iodide perovskite. This technique entails...Here in this paper, we demonstrate a facile technique for creating the mixed formamidinium(HN = CHNH_3~+, FA~+)and methylammonium(CH_3NH_3~+, MA~+) cations in the lead iodide perovskite. This technique entails a facile drop-casting of formamidinium iodide(FAI) solutions on as-prepared MAPbI_3 perovskite thin films under the controlled conditions,which leads to controllable displacement of the MA~+ cations by FA~+ cations in the perovskite structure at room temperature. Uniform and controllable mixed organic cation perovskite thin films without a "bi-layered" or graded structure are achieved. By applying this approach to photovoltaic devices, we are able to improve the performances of devices through extending their optical-absorption onset further into the infrared region to enhance solar-light harvesting. Additionally,this work provides a simple and efficient technique to tune the structural, electrical, and optoelectronic properties of the light-harvesting materials for high-performance perovskite solar cells.展开更多
Zeolitic material as Na-mordenit (SiO<sub>2</sub>/Al<sub>2</sub>O<sub>3</sub> = 10) was synthesized on the basis of natural raw material volcanic ash, in presence of organic compone...Zeolitic material as Na-mordenit (SiO<sub>2</sub>/Al<sub>2</sub>O<sub>3</sub> = 10) was synthesized on the basis of natural raw material volcanic ash, in presence of organic components tetraetilamonium iodide (TEAI). The ash sample used in the laboratory experiments contains 67%, 56% SiO<sub>2</sub> and 12.48% Al<sub>2</sub>O<sub>3</sub>, abundances. The reaction time as well as the influence of TEAI was studied in the zeolitic materials crystallization. The experiments were carried out under hydrothermal conditions, autogenic pressure and temperature of 220℃, as well as reaction time from 48 to 240 h. Products from this hydrothermal treatment were identified by the rentgenophase analysis methods on the apparatus of BRUKER D2 PHASER and weight-spectroscopic analysis method on the apparatus of ICP-MS Agilent 7700. Of the zeolitic material, the Na-mordenit zeolite was found to be the most effective for the retention of cations Pb<sup>2+</sup>, Zn<sup>2+</sup> and Ba<sup>2+</sup>.展开更多
AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A to...AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A total of 61 patients with Crohn's disease (CD), 151 patients with ulcerative colitis (UC), and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction (PCR-SSP) or by restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 (0/61 with CD) and 1.3% (2/151 with UC). CONCLUSION: Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.展开更多
AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). MET...AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.展开更多
MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte...MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].展开更多
Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal...Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid X receptor(FXR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.展开更多
AIM: To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier (SLC) transporters.METHODS: Various SLC transporters including the essential human organic anion...AIM: To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier (SLC) transporters.METHODS: Various SLC transporters including the essential human organic anion transporter 1 (OAT1), OAT2, OAT3 and OAT4 as well as the important organic cation transporter 1 (OCTN1) and OCTN2, were over-expressed in human embryonic kidney (HEK)-293 cells, a well-established cell model of transporter studies. Transport uptake assay was performed 24 h after the transfection. The transport activity was assessed with the uptake of previously determined transporter model substrates and the inhibitory effect of apigenin and kaempferol was evaluated with the substrate uptake in the presence of 10 μmol/L of each compound. Uptake measurements with varying concentrations of inhibitors (ranged from 0.0001 to 50 μmol/L) were performed to further characterize the inhibitory potency of apigenin and kaempferol. The IC50 value (the concentration that inhibits 50% of the transporter function) of each com-pound was then calculated by the nonlinear regression model of Graphpad Prism 6.0 software.RESULTS: Our data indicated that apigenin could potently inhibit the uptake of estrone-3-sulfate (ES) mediated by the HEK-293 cells expressing OAT2, OAT3 and OAT4 as well as the L-ergothioneine uptake via OCTN1-expressing HEK-293 cells. Among these trans-porters, the most prominent inhibition of apigenin was observed in the case of OAT3. Kaempferol showed sig-nifcant inhibitory effects on the uptake of ES mediated through OAT2 and OAT3. Impaired L-ergothioneine uptake due to the presence of kaempferol was also ob-served in OCTN1-expressing HEK-293 cells. Similar to apigenin, kaempferol showed the most potent inhibito-ry effect on OAT3 as well. To further assess the inhibi-tory potencies of these two compounds on the uptake of ES mediated by OAT3-expressing HEK-293 cells, their IC50 values were then determined. Both chemicals showed pronounced inhibitory potencies on OAT3 with the IC50 values of 1.7 ± 0.1 and 1.0 ± 0.1 μmol/L (P 〈 0.01) for apigenin and kaempferol, respectively.CONCLUSION: Both apigenin and kaempferol are po-tent inhibitors of OAT3; precautions will be necessary when co-administrating them with drugs that are sub-strates of OAT3.展开更多
Perovskite solar cells(PSCs)have attracted much attention due to their rapidly increased power conversion efficiencies,however,their inherent poor long-term stability hinders their commercialization.The degradation of...Perovskite solar cells(PSCs)have attracted much attention due to their rapidly increased power conversion efficiencies,however,their inherent poor long-term stability hinders their commercialization.The degradation of PSCs first comes from the degradation of hole transport materials(HTMs).Here,we report the construction of periodicπ-columnar arrays and ionic interfaces over the skeletons by introducing cationic covalent organic frameworks(C-COFs)to the HTM.Periodicπ-columnar arrays can optimize the charge transport ability and energy levels of the hole transport layer and suppress the degradation of HTM,and ionic interfaces over the skeletons can produce stronger electric dipole and electrostatic interactions,as well as higher charge densities.The C-COFs were designed and synthesized via Schiff base reaction by using 1,3,5-triformylphloroglucinol as a neutral knot and dimidium bromide as cationic linker.The neutral COFs(N-COFs)were also synthesized as a reference by using 3,8-diamino-6-phenylphenanthridine as neutral linker.PSCs with cationic COF exhibit the highest efficiency of 23.4%with excellent humidity and thermal stability.To the best of our knowledge,this is the highest efficiency among the meso-structured PSCs fabricated by a sequential process.展开更多
Modified soils(MSs) are being increasingly used as geo-engineering materials for the sedimentation removal of cyanobacterial blooms. Cationic starch(CS) has been tested as an effective soil modifier, but little is...Modified soils(MSs) are being increasingly used as geo-engineering materials for the sedimentation removal of cyanobacterial blooms. Cationic starch(CS) has been tested as an effective soil modifier, but little is known about its potential impacts on the treated water.This study investigated dissolved organic matters in the bloom water after algal removal using cationic starch modified soils(CS-MSs). Results showed that the dissolved organic carbon(DOC) could be decreased by CS-MS flocculation and the use of higher charge density CS yielded a greater DOC reduction. When CS with the charge density of 0.052, 0.102 and0.293 meq/g were used, DOC was decreased from 3.4 to 3.0, 2.3 and 1.7 mg/L, respectively.The excitation–emission matrix fluorescence spectroscopy and UV254 analysis indicated that CS-MS exhibits an ability to remove some soluble organics, which contributed to the DOC reduction. However, the use of low charge density CS posed a potential risk of DOC increase due to the high CS loading for effective algal removal. When CS with the charge density of 0.044 meq/g was used, DOC was increased from 3.4 to 3.9 mg/L. This study suggested, when CS-MS is used for cyanobacterial bloom removal, the content of dissolved organic matters in the treated water can be controlled by optimizing the charge density of CS. For the settled organic matters, other measures(e.g., capping treatments using oxygen loaded materials) should be jointly applied after algal flocculation.展开更多
The D-quadrant organizer sets up the dorsal–ventral(DV)axis and regulates mesodermal development of spiralians.Studies have revealed an important role of mitogen-activated protein kinase(MAPK)signaling in organizer f...The D-quadrant organizer sets up the dorsal–ventral(DV)axis and regulates mesodermal development of spiralians.Studies have revealed an important role of mitogen-activated protein kinase(MAPK)signaling in organizer function,but the related molecules have not been fully revealed.The association between fibroblast growth factor receptor(FGFR)and MAPK signaling in regulating organizer specification has been established in the annelid Owenia fusiformis.Now,comparable studies in other spiralian phyla are required to decipher whether this organizer-inducing function of FGFR is prevalent in Spiralia.Here,we indicate that treatment with the FGFR inhibitor SU5402 resulted in deficiency of organizer specification in the mollusk Lottia peitaihoensis.Subsequently,the bone morphogenetic protein(BMP)signaling gradient and DV patterning were disrupted,suggesting the roles of FGFR in regulating organizer function.Changes in multiple aspects of organizer function(the morphology of vegetal blastomeres,BMP signaling gradient,expression of DV patterning markers,etc.)indicate that these developmental functions have different sensitivities to FGFR/MAPK signaling.Our results reveal a functional role of FGFR in organizer specification as well as DV patterning of Lottia embryos,which expands our knowledge of spiralian organizers.展开更多
^(99)Tc is a long-lived radionuclide present in large amounts as TcO_(4)^(-)-anion in used nuclear fuel.Its removal from the waste stream is highly desirable because of its interference capability with actinide separa...^(99)Tc is a long-lived radionuclide present in large amounts as TcO_(4)^(-)-anion in used nuclear fuel.Its removal from the waste stream is highly desirable because of its interference capability with actinide separation and its volatile nature during the nuclear waste vitrification process.Despite the progress achieved in the past few years,the design of anion-exchange materials with optimized Tc uptake property and improved stability under the extreme condition is still a research goal beneficial for reducing the volume of secondary radioactive solid waste generated during the waste partitioning process.However,their design philosophy remains elusive,with challenges coming from charge repulsion,steric hindrance,and insufficient reactive sites within the materials.Herein,we present a design philosophy of cationic polymer network materials for TcO_(4)^(-)separation by systematic precursor screening and structure prediction.This affords an optimized material,SCU-CPN-2(SCU=Soochow University),with extremely high positive charge density while maintaining high radiation resistance.SCU-CPN-2 exhibits a record high adsorption capacity1,467 mg/g towards the surrogate ReO_(4)^(-)compared to all anion-exchange materials reported up to date.In addition to ultrafast adsorption kinetics,SCU-CPN-2 has remarkable selectivity over nitrate and sulfate,and facile recyclability.展开更多
The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelle...The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2(OCTN2) were constructed by combining carnitine conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(Car-PEOz-PLA) with monomethoxy poly(ethylene glycol)-poly(D,L-lactide)(mP EG-PLA). The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.展开更多
基金supported by the National Natural Science Foundation of China (Nos.21938005 and 21905206)。
文摘Ion diffusion kinetics,depending on the size,tortuosity,connectivity of the channels,greatly affects the rate performance of the electrodes.Two-dimensional materials(2DMs) has emerged as promising electrode materials in the past decades.Howeve r,the applications of 2DMs electrodes are limited by the strong restacking problem,which leads to a poor rate capability.In this work,we for the first time mediated the mo rphology of molybdenum disulfide(MoS_(2)) nanosheets via a facile coagulation method;abundant sheet crumples were induced,which greatly enhance their surface accessibility and thus benefit the ion diffusion kinetics.Consequently,the crumpled-MoS_(2) electrodes follow a capacitive Na-ion charge-storage mechanism to a large extent.Importantly,we demonstrate the special role of organic cations in the inter-sheet assembly configuration,in sharp contrast with that of alkali/alkaline-earth ones.We propose that organic cations cause edge/face contact of the sheets,instead of the face/face contact,thus affording a house-of-cards structure.
基金Project supported by the Fundamental Research Funds for the Central Universities,China(Grant No.2015QNA09)
文摘Here in this paper, we demonstrate a facile technique for creating the mixed formamidinium(HN = CHNH_3~+, FA~+)and methylammonium(CH_3NH_3~+, MA~+) cations in the lead iodide perovskite. This technique entails a facile drop-casting of formamidinium iodide(FAI) solutions on as-prepared MAPbI_3 perovskite thin films under the controlled conditions,which leads to controllable displacement of the MA~+ cations by FA~+ cations in the perovskite structure at room temperature. Uniform and controllable mixed organic cation perovskite thin films without a "bi-layered" or graded structure are achieved. By applying this approach to photovoltaic devices, we are able to improve the performances of devices through extending their optical-absorption onset further into the infrared region to enhance solar-light harvesting. Additionally,this work provides a simple and efficient technique to tune the structural, electrical, and optoelectronic properties of the light-harvesting materials for high-performance perovskite solar cells.
文摘Zeolitic material as Na-mordenit (SiO<sub>2</sub>/Al<sub>2</sub>O<sub>3</sub> = 10) was synthesized on the basis of natural raw material volcanic ash, in presence of organic components tetraetilamonium iodide (TEAI). The ash sample used in the laboratory experiments contains 67%, 56% SiO<sub>2</sub> and 12.48% Al<sub>2</sub>O<sub>3</sub>, abundances. The reaction time as well as the influence of TEAI was studied in the zeolitic materials crystallization. The experiments were carried out under hydrothermal conditions, autogenic pressure and temperature of 220℃, as well as reaction time from 48 to 240 h. Products from this hydrothermal treatment were identified by the rentgenophase analysis methods on the apparatus of BRUKER D2 PHASER and weight-spectroscopic analysis method on the apparatus of ICP-MS Agilent 7700. Of the zeolitic material, the Na-mordenit zeolite was found to be the most effective for the retention of cations Pb<sup>2+</sup>, Zn<sup>2+</sup> and Ba<sup>2+</sup>.
基金Doctoral Natural Science Fund of Guangdong Province, China, No. 04300361
文摘AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A total of 61 patients with Crohn's disease (CD), 151 patients with ulcerative colitis (UC), and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction (PCR-SSP) or by restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 (0/61 with CD) and 1.3% (2/151 with UC). CONCLUSION: Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.
文摘AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.
基金supported by"H+Die Spitaler der Schweiz" the Swiss Agency for Development and Cooperation(DEZA)by the University Hospital Zurich/Switzerland
文摘MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].
基金supported by the National Natural Science Foundation of China(Nos.82173884,81872930,82073922 and 81872833)the“Double First-Class”university project(No.CPU2018GY22,China)。
文摘Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid X receptor(FXR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.
基金Supported by Internal funding from Faculty of Pharmacy,the University of Sydney,Australia
文摘AIM: To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier (SLC) transporters.METHODS: Various SLC transporters including the essential human organic anion transporter 1 (OAT1), OAT2, OAT3 and OAT4 as well as the important organic cation transporter 1 (OCTN1) and OCTN2, were over-expressed in human embryonic kidney (HEK)-293 cells, a well-established cell model of transporter studies. Transport uptake assay was performed 24 h after the transfection. The transport activity was assessed with the uptake of previously determined transporter model substrates and the inhibitory effect of apigenin and kaempferol was evaluated with the substrate uptake in the presence of 10 μmol/L of each compound. Uptake measurements with varying concentrations of inhibitors (ranged from 0.0001 to 50 μmol/L) were performed to further characterize the inhibitory potency of apigenin and kaempferol. The IC50 value (the concentration that inhibits 50% of the transporter function) of each com-pound was then calculated by the nonlinear regression model of Graphpad Prism 6.0 software.RESULTS: Our data indicated that apigenin could potently inhibit the uptake of estrone-3-sulfate (ES) mediated by the HEK-293 cells expressing OAT2, OAT3 and OAT4 as well as the L-ergothioneine uptake via OCTN1-expressing HEK-293 cells. Among these trans-porters, the most prominent inhibition of apigenin was observed in the case of OAT3. Kaempferol showed sig-nifcant inhibitory effects on the uptake of ES mediated through OAT2 and OAT3. Impaired L-ergothioneine uptake due to the presence of kaempferol was also ob-served in OCTN1-expressing HEK-293 cells. Similar to apigenin, kaempferol showed the most potent inhibito-ry effect on OAT3 as well. To further assess the inhibi-tory potencies of these two compounds on the uptake of ES mediated by OAT3-expressing HEK-293 cells, their IC50 values were then determined. Both chemicals showed pronounced inhibitory potencies on OAT3 with the IC50 values of 1.7 ± 0.1 and 1.0 ± 0.1 μmol/L (P 〈 0.01) for apigenin and kaempferol, respectively.CONCLUSION: Both apigenin and kaempferol are po-tent inhibitors of OAT3; precautions will be necessary when co-administrating them with drugs that are sub-strates of OAT3.
基金This work was supported by the National Natural Science Foundation of China(No.52203359)Fundamental Research Funds for the Central Universities(No.NS2022092)+5 种基金National Key Research and Development Program of China(No.2019YFA0705400)Natural Science Foundation of Jiangsu Province(No.BK20212008)the Research Fund of State Key Laboratory of Mechanics and Control of Mechanical Structures(Nos.MCMS-I-0421K01 and MCMS-I-0422K01)the Fundamental Research Funds for the Central Universities(No.NJ2022002)the National Natural Science Foundation of China(Nos.52073119 and 21774040)A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Perovskite solar cells(PSCs)have attracted much attention due to their rapidly increased power conversion efficiencies,however,their inherent poor long-term stability hinders their commercialization.The degradation of PSCs first comes from the degradation of hole transport materials(HTMs).Here,we report the construction of periodicπ-columnar arrays and ionic interfaces over the skeletons by introducing cationic covalent organic frameworks(C-COFs)to the HTM.Periodicπ-columnar arrays can optimize the charge transport ability and energy levels of the hole transport layer and suppress the degradation of HTM,and ionic interfaces over the skeletons can produce stronger electric dipole and electrostatic interactions,as well as higher charge densities.The C-COFs were designed and synthesized via Schiff base reaction by using 1,3,5-triformylphloroglucinol as a neutral knot and dimidium bromide as cationic linker.The neutral COFs(N-COFs)were also synthesized as a reference by using 3,8-diamino-6-phenylphenanthridine as neutral linker.PSCs with cationic COF exhibit the highest efficiency of 23.4%with excellent humidity and thermal stability.To the best of our knowledge,this is the highest efficiency among the meso-structured PSCs fabricated by a sequential process.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA09030203)the Science Promotion Program of Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (No. YSW2013B05)
文摘Modified soils(MSs) are being increasingly used as geo-engineering materials for the sedimentation removal of cyanobacterial blooms. Cationic starch(CS) has been tested as an effective soil modifier, but little is known about its potential impacts on the treated water.This study investigated dissolved organic matters in the bloom water after algal removal using cationic starch modified soils(CS-MSs). Results showed that the dissolved organic carbon(DOC) could be decreased by CS-MS flocculation and the use of higher charge density CS yielded a greater DOC reduction. When CS with the charge density of 0.052, 0.102 and0.293 meq/g were used, DOC was decreased from 3.4 to 3.0, 2.3 and 1.7 mg/L, respectively.The excitation–emission matrix fluorescence spectroscopy and UV254 analysis indicated that CS-MS exhibits an ability to remove some soluble organics, which contributed to the DOC reduction. However, the use of low charge density CS posed a potential risk of DOC increase due to the high CS loading for effective algal removal. When CS with the charge density of 0.044 meq/g was used, DOC was increased from 3.4 to 3.9 mg/L. This study suggested, when CS-MS is used for cyanobacterial bloom removal, the content of dissolved organic matters in the treated water can be controlled by optimizing the charge density of CS. For the settled organic matters, other measures(e.g., capping treatments using oxygen loaded materials) should be jointly applied after algal flocculation.
基金supported by the National Natural Science Foundation of China(grant numbers 42206092,42076123)the Earmarked Fund for China Agriculture Research System(grant number CARS-49)the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.LSKJ202203002).
文摘The D-quadrant organizer sets up the dorsal–ventral(DV)axis and regulates mesodermal development of spiralians.Studies have revealed an important role of mitogen-activated protein kinase(MAPK)signaling in organizer function,but the related molecules have not been fully revealed.The association between fibroblast growth factor receptor(FGFR)and MAPK signaling in regulating organizer specification has been established in the annelid Owenia fusiformis.Now,comparable studies in other spiralian phyla are required to decipher whether this organizer-inducing function of FGFR is prevalent in Spiralia.Here,we indicate that treatment with the FGFR inhibitor SU5402 resulted in deficiency of organizer specification in the mollusk Lottia peitaihoensis.Subsequently,the bone morphogenetic protein(BMP)signaling gradient and DV patterning were disrupted,suggesting the roles of FGFR in regulating organizer function.Changes in multiple aspects of organizer function(the morphology of vegetal blastomeres,BMP signaling gradient,expression of DV patterning markers,etc.)indicate that these developmental functions have different sensitivities to FGFR/MAPK signaling.Our results reveal a functional role of FGFR in organizer specification as well as DV patterning of Lottia embryos,which expands our knowledge of spiralian organizers.
基金supported by the National Natural Science Foundation of China(21790374,21825601,21806117,21906114,22006108)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the National Key R&D Program of China(2018YFB1900203)。
文摘^(99)Tc is a long-lived radionuclide present in large amounts as TcO_(4)^(-)-anion in used nuclear fuel.Its removal from the waste stream is highly desirable because of its interference capability with actinide separation and its volatile nature during the nuclear waste vitrification process.Despite the progress achieved in the past few years,the design of anion-exchange materials with optimized Tc uptake property and improved stability under the extreme condition is still a research goal beneficial for reducing the volume of secondary radioactive solid waste generated during the waste partitioning process.However,their design philosophy remains elusive,with challenges coming from charge repulsion,steric hindrance,and insufficient reactive sites within the materials.Herein,we present a design philosophy of cationic polymer network materials for TcO_(4)^(-)separation by systematic precursor screening and structure prediction.This affords an optimized material,SCU-CPN-2(SCU=Soochow University),with extremely high positive charge density while maintaining high radiation resistance.SCU-CPN-2 exhibits a record high adsorption capacity1,467 mg/g towards the surrogate ReO_(4)^(-)compared to all anion-exchange materials reported up to date.In addition to ultrafast adsorption kinetics,SCU-CPN-2 has remarkable selectivity over nitrate and sulfate,and facile recyclability.
基金The National Natural Science Foundation of China(Grant No.81673366)the National Key Science Research Program of China(973 Program,Grant No.2015CB932100)
文摘The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2(OCTN2) were constructed by combining carnitine conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(Car-PEOz-PLA) with monomethoxy poly(ethylene glycol)-poly(D,L-lactide)(mP EG-PLA). The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.