Three new halimane furanoditerpenoids(1-3)and three new clerodane furanoditerpenoids(4-6),along with seven known terpenoids including four pimarane diterpenoids(7-10)and three norisoprenoids(11-13)were isolated from t...Three new halimane furanoditerpenoids(1-3)and three new clerodane furanoditerpenoids(4-6),along with seven known terpenoids including four pimarane diterpenoids(7-10)and three norisoprenoids(11-13)were isolated from the 95%EtOH extracts of the plants of Croton cnidophyllus.The 2D structures including absolute configuration of new furanoditerpenoids(1-6)were elucidated by analysis of their HRMS and NMR data as well as comparison of experi-mental and calculated ECD curves.Bioassay revealed that two compounds(8 and 9)possessed certain inhibitory effects against NO production stimulated by LPS,with IC_(50) values of 19.00±1.76 and 21.61±1.11μM,respectively.展开更多
Photocatalysis is considered as an ideal strategy for water pollution treatment.However,it remains challenging to design a highly efficient photo-catalytic system through regulating the charge flow via a precise appro...Photocatalysis is considered as an ideal strategy for water pollution treatment.However,it remains challenging to design a highly efficient photo-catalytic system through regulating the charge flow via a precise approach.In this work,a novel NH2-MIL-125(Ti)/Bi2WO6 composite was constructed via self-assembly growing Bi2WO6 nanosheets on NH2-MIL-125(Ti)material.The characterization results demonstrated that NH2-MIL-125(Ti)was successfully incorporated into Bi2WO6 and the photoexcited carriers could be efficiently separated and transferred between the two components.NH2-MIL-125(Ti)/Bi2WO6 composites displayed enhanced photocatalytic activity for the removal of rhodamine B(RhB)and tetracycline(TC)under visible light irradiation,and the optimal weight ratio of NH2-MIL-125(Ti)was determined to be 7 wt%.The introduction of NH2-MIL-125(Ti)into Bi2WO6 could raise the absorption of visible light,accelerate the separation and transfer of charge carriers,and boost photocatalytic activity.This research presents a wide range of possibilities for the further development of novel composites in the field of environment purification.展开更多
Mulberry Diels-Alder-type adducts(MDAAs)are unique phenolic natural products biosynthetically derived from the intermolecular[4+2]-cycloaddition of dienophiles(mainly chalcones)and dehydroprenylphenol dienes,which are...Mulberry Diels-Alder-type adducts(MDAAs)are unique phenolic natural products biosynthetically derived from the intermolecular[4+2]-cycloaddition of dienophiles(mainly chalcones)and dehydroprenylphenol dienes,which are exclusively distributed in moraceous plants.A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980.Structurally,the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups(Types A−H),while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs(Type I).These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures,remarkable biological activities,and synthetic challenges.The present review provides a comprehensive summary of the structural properties,bioactivities,and syntheses of MDAAs.Cited references were collected between 1980 and 2021 from the SciFinder,Web of Science,and China National Knowledge Internet(CNKI).展开更多
A selective, sensitive, and convenient assay for human collagenase is required because of its implication in diseases such as rheumatoid arthritis, osteoarthritis, and tumors. Here, a novel assay for human collagenase...A selective, sensitive, and convenient assay for human collagenase is required because of its implication in diseases such as rheumatoid arthritis, osteoarthritis, and tumors. Here, a novel assay for human collagenase activity is described in which enzymatic degradation of native collagen or acetyl peptide is determined by using a fluorogenic reaction for oligopeptides. The oligopeptides are quantified spectrofluorometrically with either 3,4-dihydroxyphenylacetic acid or 1,2-dihydroxybenzen reaction in the presence of sodium periodate and sodium borate (pH 7 - 8). These reactions can selectively convert N-terminal Gly-containing oligopeptides and N-terminal Ile-containing oligopeptides to fluorescence (FL) compounds, respectively, but not proteins, acetyl peptides or amino acids. Under optimized conditions using 1.65 μM collagen IV or 1.5 mM Ac-GPQGI- AGQ as substrates, this assay exhibits a proportional relationship between FL intensities and human collagenase-3 (MMP-13) concentrations. It can assay endogenous collagenase activities in several biological samples, such as cultured human cells and cheek tissue.展开更多
Increasing the utilization efficiency of photogenerated electrons is highly recognized as one of the ef-ficient approaches to boost the photocatalytic CO_(2)conversion efficiency.Herein,ZIF-67-derived porous carbon(PC...Increasing the utilization efficiency of photogenerated electrons is highly recognized as one of the ef-ficient approaches to boost the photocatalytic CO_(2)conversion efficiency.Herein,ZIF-67-derived porous carbon(PC)material was employed for the construction of PC@ultrafine Bi_(12)O_(17)Br_(2)nanotubes(PC@BOB NTs)composites through a facile solvothermal synthesis in order to optimize the use of excited elec-trons in the BOB NTs.Photoelectrochemical characterization results revealed that the introduction of PC material achieved a faster charge separation rate in the PC@BOB composites,ensuring more photogener-ated electrons participate in the CO_(2)adsorption and activation process.Moreover,the pore structures of ZIF-67-derived PC material provided abundant confined spaces for the enrichment of CO_(2)molecules.Af-ter 5 h of Xenon lamp irradiation,PC@BOB composites exhibited obviously increased photocatalytic CO_(2)reduction activity in the pure water.When the addition amount of PC was 5 wt%,the PC@BOB-2 com-posite showed the highest CO evolution rate of 359.70μmol/g,which was 2.95 times higher than that of the pure BOB NTs.This work provides some independent insights into the applications of Metal-Organic Framework(MOF)-derived hierarchical porous structures to strengthen the CO_(2)enrichment,as well as the excited charge utilization efficiency,thus achieving a high solar-to-fuel conversion efficiency.展开更多
(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01....(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.展开更多
Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after i...Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.展开更多
Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers.However,the lack of druggable inhibitors restricts its therapeutic proof of concept.In the present work,...Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers.However,the lack of druggable inhibitors restricts its therapeutic proof of concept.In the present work,we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability(>25 folds)and oral bioavailability.DD1-Br inhibited the survival of castration-resistant prostate cancer(CRPC)cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy(0.5 mg/kg)and in enzalutamidecombination therapy.Mechanistic study revealed that by targeting importin-β1,DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers,particularly AR-V7,a main contributor to enzalutamide resistance,leading to the integral suppression of downstream oncogenic signaling.This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.展开更多
Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod...Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.展开更多
In traditional body-centered cubic(bcc)metals,the core properties of screw dislocations play a critical role in plastic deformation at low temperatures.Recently,much attention has been focused on refractory high-entro...In traditional body-centered cubic(bcc)metals,the core properties of screw dislocations play a critical role in plastic deformation at low temperatures.Recently,much attention has been focused on refractory high-entropy alloys(RHEAs),which also possess bcc crystal structures.However,unlike face-centered cubic high-entropy alloys(HEAs),there have been far fewer investigations into bcc HEAs,specifically on the possible effects of chemical short-range order(SRO)in these multiple principal element alloys on dislocation mobility.Here,using density functional theory,we investigate the distribution of dislocation core properties in MoNbTaW RHEAs alloys,and how they are influenced by SRO.The average values of the core energies in the RHEA are found to be larger than those in the corresponding pure constituent bcc metals,and are relatively insensitive to the degree of SRO.However,the presence of SRO is shown to have a large effect on narrowing the distribution of dislocation core energies and decreasing the spatial heterogeneity of dislocation core energies in the RHEA.It is argued that the consequences of the mechanical behavior of HEAs is a change in the energy landscape of the dislocations,which would likely heterogeneously inhibit their motion.展开更多
In this paper, ATLAS 2D device simulator of SILVACO was used for device simulation of inverted- staggered thin film transistor using amorphous indium gallium zinc oxide as active layer (a-IGZO-TFT) with double activ...In this paper, ATLAS 2D device simulator of SILVACO was used for device simulation of inverted- staggered thin film transistor using amorphous indium gallium zinc oxide as active layer (a-IGZO-TFT) with double active layers, based on the density of states (DOS) model of amorphous material. The change of device performance induced by the thickness variation of each active layer was studied, and the interface between double active layers was analyzed. The best performance was found when the interface was near the edge of the channel, by optimizing the thickness of each active layers, the high performance device of threshold voltage (Vth) = -0.89 V, sub-threshold swing (SS)= 0.27, on/off current ratio (IoN/IoFF) = 6.98 × 10^14 was obtained.展开更多
Novel carbon quantum dots(CQDs)/Bi OBr composite photocatalysts have been constructed through a facile hydrothermal synthesis in the presence of ionic liquid 1-hexadecyl-3-methylimidazolium bromide([C16 mim]Br). S...Novel carbon quantum dots(CQDs)/Bi OBr composite photocatalysts have been constructed through a facile hydrothermal synthesis in the presence of ionic liquid 1-hexadecyl-3-methylimidazolium bromide([C16 mim]Br). Series of characterizations have been performed to confirm the uniform distribution of CQDs in Bi OBr nanosheets and the synergistic effect for photocatalytic degradation organic pollutants between CQDs and Bi OBr. The results show that 3.1 wt% CQDs/Bi OBr photocatalyst possesses the best photocatalytic activity for the degradation of colorless antibiotic tetracycline(TC), endocrine disrupter bisphenol A(BPA) and dye rhodamine B(Rh B), under visible light irradiation, which exhibited the highest photocatalytic performance. The enhanced photocatalytic performance for CQDs/Bi OBr composites could be attributed to the wider optical absorption range and fast separation of photogenerated charge carriers after the introduction of CQDs. The key roles of CQDs for the enhanced photocatalytic activity of Bi OBr have been discussed. A possible mechanism of CQDs/Bi OBr on the enhancement of visible light performance was proposed.展开更多
Textured surface boron-doped zinc oxide (BZO) thin films were fabricated by metal organic chemical vapor deposition as transparent conductive oxide (TCO) for solar cells. The surface microstructure was characteriz...Textured surface boron-doped zinc oxide (BZO) thin films were fabricated by metal organic chemical vapor deposition as transparent conductive oxide (TCO) for solar cells. The surface microstructure was characterized by X-ray diffraction spectrum and scan- ning electron microscope. The optical transmittance was shown by optical transmittance microscope and the electrical properties were tested by Hall measurements. The thickness of the BZO film has crucial impact on the surface morphology, optical transmittance, and resistivity. The electrical and optical properties as well as surface microstructure varied inconsistently with the increase of the film thickness. The grain size and the surface roughness increased with the increase of the film thickness. The conductivity increased from 0.96x 103 tO 6.94x 103 S/cm while the optical transmittance decreased from above 85% to nearly 80% with the increase of film thickness from 195 to 1021 nm. The BZO films deposited as both front and back transparent electrodes were applied to the bifacial p- type a-Si:H/i-type a-Si:H/n-type c-Si/i-type a-Si:H/n+-type a-Si:H heterojunction solar cells to obtain the optimized parameter of thickness. The highest efficiency of all the samples was 17.8% obtained with the BZO film thickness of 829 nm. Meanwhile, the fill factor was 0.676, the open- circuit voltage was 0.63 Vand the short-circuit density was 41.79 mA/cm2. The properties of the solar cells changing with the thickness were also investigated.展开更多
基金the National Natural Science Foundation of China(No.82273804)the Science and Technology Program of Guangzhou,China(No.202201011613)+3 种基金the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(No.SML2021SP301)the Open Program of Shenzhen Bay Laboratory(No.SZBL2021080601007)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y093)the Guangdong Basic and Applied Basic Research Foundation,China(No.2021B1515140062).
文摘Three new halimane furanoditerpenoids(1-3)and three new clerodane furanoditerpenoids(4-6),along with seven known terpenoids including four pimarane diterpenoids(7-10)and three norisoprenoids(11-13)were isolated from the 95%EtOH extracts of the plants of Croton cnidophyllus.The 2D structures including absolute configuration of new furanoditerpenoids(1-6)were elucidated by analysis of their HRMS and NMR data as well as comparison of experi-mental and calculated ECD curves.Bioassay revealed that two compounds(8 and 9)possessed certain inhibitory effects against NO production stimulated by LPS,with IC_(50) values of 19.00±1.76 and 21.61±1.11μM,respectively.
基金Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJ1500933)Chongqing Research Program of Basic Research and Frontier Technology(cstc2017jcyjA0834)Chongqing Key Industries Common Key Technology Innovation Program(cstc2015zdcy-ztzx60013)
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21476098,21471069 and 21576123)and Jiangsu University Scientific Research Funding(No.11JDG0146).
文摘Photocatalysis is considered as an ideal strategy for water pollution treatment.However,it remains challenging to design a highly efficient photo-catalytic system through regulating the charge flow via a precise approach.In this work,a novel NH2-MIL-125(Ti)/Bi2WO6 composite was constructed via self-assembly growing Bi2WO6 nanosheets on NH2-MIL-125(Ti)material.The characterization results demonstrated that NH2-MIL-125(Ti)was successfully incorporated into Bi2WO6 and the photoexcited carriers could be efficiently separated and transferred between the two components.NH2-MIL-125(Ti)/Bi2WO6 composites displayed enhanced photocatalytic activity for the removal of rhodamine B(RhB)and tetracycline(TC)under visible light irradiation,and the optimal weight ratio of NH2-MIL-125(Ti)was determined to be 7 wt%.The introduction of NH2-MIL-125(Ti)into Bi2WO6 could raise the absorption of visible light,accelerate the separation and transfer of charge carriers,and boost photocatalytic activity.This research presents a wide range of possibilities for the further development of novel composites in the field of environment purification.
基金supported by the National Natural Science Foundation of China (Nos.81973203 and 81973195)the Guangdong Basic and Applied Basic Research Foundation,China (No.2020A1515010841)+2 种基金the Open Program of Shenzhen Bay Laboratory (No.SZBL2021080601007)the Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (No.SML2021SP301)the Key-Area Research and Development Program of Guangdong Province,China (No.2020B1111110003).
文摘Mulberry Diels-Alder-type adducts(MDAAs)are unique phenolic natural products biosynthetically derived from the intermolecular[4+2]-cycloaddition of dienophiles(mainly chalcones)and dehydroprenylphenol dienes,which are exclusively distributed in moraceous plants.A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980.Structurally,the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups(Types A−H),while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs(Type I).These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures,remarkable biological activities,and synthetic challenges.The present review provides a comprehensive summary of the structural properties,bioactivities,and syntheses of MDAAs.Cited references were collected between 1980 and 2021 from the SciFinder,Web of Science,and China National Knowledge Internet(CNKI).
文摘A selective, sensitive, and convenient assay for human collagenase is required because of its implication in diseases such as rheumatoid arthritis, osteoarthritis, and tumors. Here, a novel assay for human collagenase activity is described in which enzymatic degradation of native collagen or acetyl peptide is determined by using a fluorogenic reaction for oligopeptides. The oligopeptides are quantified spectrofluorometrically with either 3,4-dihydroxyphenylacetic acid or 1,2-dihydroxybenzen reaction in the presence of sodium periodate and sodium borate (pH 7 - 8). These reactions can selectively convert N-terminal Gly-containing oligopeptides and N-terminal Ile-containing oligopeptides to fluorescence (FL) compounds, respectively, but not proteins, acetyl peptides or amino acids. Under optimized conditions using 1.65 μM collagen IV or 1.5 mM Ac-GPQGI- AGQ as substrates, this assay exhibits a proportional relationship between FL intensities and human collagenase-3 (MMP-13) concentrations. It can assay endogenous collagenase activities in several biological samples, such as cultured human cells and cheek tissue.
基金supported by the National Natural Science Foundation of China(Nos.22108108,22108106,22109055)China Postdoctoral Science Foundation(No.2022M721381).
文摘Increasing the utilization efficiency of photogenerated electrons is highly recognized as one of the ef-ficient approaches to boost the photocatalytic CO_(2)conversion efficiency.Herein,ZIF-67-derived porous carbon(PC)material was employed for the construction of PC@ultrafine Bi_(12)O_(17)Br_(2)nanotubes(PC@BOB NTs)composites through a facile solvothermal synthesis in order to optimize the use of excited elec-trons in the BOB NTs.Photoelectrochemical characterization results revealed that the introduction of PC material achieved a faster charge separation rate in the PC@BOB composites,ensuring more photogener-ated electrons participate in the CO_(2)adsorption and activation process.Moreover,the pore structures of ZIF-67-derived PC material provided abundant confined spaces for the enrichment of CO_(2)molecules.Af-ter 5 h of Xenon lamp irradiation,PC@BOB composites exhibited obviously increased photocatalytic CO_(2)reduction activity in the pure water.When the addition amount of PC was 5 wt%,the PC@BOB-2 com-posite showed the highest CO evolution rate of 359.70μmol/g,which was 2.95 times higher than that of the pure BOB NTs.This work provides some independent insights into the applications of Metal-Organic Framework(MOF)-derived hierarchical porous structures to strengthen the CO_(2)enrichment,as well as the excited charge utilization efficiency,thus achieving a high solar-to-fuel conversion efficiency.
基金National Natural Science Foundation of China(Nos.U20A2001,81973195,21877133)the Guangdong Marine Economy Development Special Project(Nos.GDNRC[2022]35,GDNRC[2023]39)。
文摘(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.
基金funded by the National Key R&D Program of China(No.2020YFA0908100)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(Nos.JNL2022004A,JNL2022019B)Shandong Provincial Laboratory Project(No.SYS202202).
文摘Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.
基金supported by the Natural Science Foundation of China(Nos.82273804,81973195,81872891,and 81973203)the Southerm Marine Science and Engineering Guangdong Laboratory(Zhuhai)(No.SML2021SP301,China)+2 种基金Open Program of Shenzhen Bay Laboratory(No.SZBL2021080601007,China)the Guangdong Natural Science Funds for Distinguished Young Scholar(No.2019B151502016,China)Guangdong-Hong Kong-Macao research team project of the Guangdong Basic and Applied Basic Research Foundation(No.2022B1515130008,China).
文摘Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers.However,the lack of druggable inhibitors restricts its therapeutic proof of concept.In the present work,we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability(>25 folds)and oral bioavailability.DD1-Br inhibited the survival of castration-resistant prostate cancer(CRPC)cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy(0.5 mg/kg)and in enzalutamidecombination therapy.Mechanistic study revealed that by targeting importin-β1,DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers,particularly AR-V7,a main contributor to enzalutamide resistance,leading to the integral suppression of downstream oncogenic signaling.This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.
基金funded by the Major Projects of the National Natural Science Foundation of China(81690261)the National Natural Science Foundation of China(81703450)the Postdoctoral Research Foundation of China(2017M620429)
文摘Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin(DOX) and Toll-like receptor 7 agonist imiquimod(IMQ) in low molecular weight heparin(LMWH)-D-α-tocopheryl succinate(TOS) micelles(LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles(LT-DOX)generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles(LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1(PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8+ CTLs/Treg and CD4+ Teff/Treg. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.
基金This work was supported by the US Department of Energy,Office of Science,Office of Basic Energy Sciences,Materials Sciences and Engineering Division,under contract no.DE-AC02-05-CH11231 within the Damage Tolerance in Structural Materials(KC 13)program.
文摘In traditional body-centered cubic(bcc)metals,the core properties of screw dislocations play a critical role in plastic deformation at low temperatures.Recently,much attention has been focused on refractory high-entropy alloys(RHEAs),which also possess bcc crystal structures.However,unlike face-centered cubic high-entropy alloys(HEAs),there have been far fewer investigations into bcc HEAs,specifically on the possible effects of chemical short-range order(SRO)in these multiple principal element alloys on dislocation mobility.Here,using density functional theory,we investigate the distribution of dislocation core properties in MoNbTaW RHEAs alloys,and how they are influenced by SRO.The average values of the core energies in the RHEA are found to be larger than those in the corresponding pure constituent bcc metals,and are relatively insensitive to the degree of SRO.However,the presence of SRO is shown to have a large effect on narrowing the distribution of dislocation core energies and decreasing the spatial heterogeneity of dislocation core energies in the RHEA.It is argued that the consequences of the mechanical behavior of HEAs is a change in the energy landscape of the dislocations,which would likely heterogeneously inhibit their motion.
文摘In this paper, ATLAS 2D device simulator of SILVACO was used for device simulation of inverted- staggered thin film transistor using amorphous indium gallium zinc oxide as active layer (a-IGZO-TFT) with double active layers, based on the density of states (DOS) model of amorphous material. The change of device performance induced by the thickness variation of each active layer was studied, and the interface between double active layers was analyzed. The best performance was found when the interface was near the edge of the channel, by optimizing the thickness of each active layers, the high performance device of threshold voltage (Vth) = -0.89 V, sub-threshold swing (SS)= 0.27, on/off current ratio (IoN/IoFF) = 6.98 × 10^14 was obtained.
基金financially supported by the National Natural Science Foundation of China (Nos. 21471069, 21476098 and 21576123)Jiangsu University Scientific Research Funding (No. 11JDG0146)Doctoral Innovation Fund of Jiangsu Province (No. KYCX17_1791)
文摘Novel carbon quantum dots(CQDs)/Bi OBr composite photocatalysts have been constructed through a facile hydrothermal synthesis in the presence of ionic liquid 1-hexadecyl-3-methylimidazolium bromide([C16 mim]Br). Series of characterizations have been performed to confirm the uniform distribution of CQDs in Bi OBr nanosheets and the synergistic effect for photocatalytic degradation organic pollutants between CQDs and Bi OBr. The results show that 3.1 wt% CQDs/Bi OBr photocatalyst possesses the best photocatalytic activity for the degradation of colorless antibiotic tetracycline(TC), endocrine disrupter bisphenol A(BPA) and dye rhodamine B(Rh B), under visible light irradiation, which exhibited the highest photocatalytic performance. The enhanced photocatalytic performance for CQDs/Bi OBr composites could be attributed to the wider optical absorption range and fast separation of photogenerated charge carriers after the introduction of CQDs. The key roles of CQDs for the enhanced photocatalytic activity of Bi OBr have been discussed. A possible mechanism of CQDs/Bi OBr on the enhancement of visible light performance was proposed.
文摘Textured surface boron-doped zinc oxide (BZO) thin films were fabricated by metal organic chemical vapor deposition as transparent conductive oxide (TCO) for solar cells. The surface microstructure was characterized by X-ray diffraction spectrum and scan- ning electron microscope. The optical transmittance was shown by optical transmittance microscope and the electrical properties were tested by Hall measurements. The thickness of the BZO film has crucial impact on the surface morphology, optical transmittance, and resistivity. The electrical and optical properties as well as surface microstructure varied inconsistently with the increase of the film thickness. The grain size and the surface roughness increased with the increase of the film thickness. The conductivity increased from 0.96x 103 tO 6.94x 103 S/cm while the optical transmittance decreased from above 85% to nearly 80% with the increase of film thickness from 195 to 1021 nm. The BZO films deposited as both front and back transparent electrodes were applied to the bifacial p- type a-Si:H/i-type a-Si:H/n-type c-Si/i-type a-Si:H/n+-type a-Si:H heterojunction solar cells to obtain the optimized parameter of thickness. The highest efficiency of all the samples was 17.8% obtained with the BZO film thickness of 829 nm. Meanwhile, the fill factor was 0.676, the open- circuit voltage was 0.63 Vand the short-circuit density was 41.79 mA/cm2. The properties of the solar cells changing with the thickness were also investigated.