Coal and gas outburst is one of the main gas hazards in coal mines. However, due to the risks of the coal and gas outburst, the field test is difficult to complete. Therefore, an effective approach to studying the mec...Coal and gas outburst is one of the main gas hazards in coal mines. However, due to the risks of the coal and gas outburst, the field test is difficult to complete. Therefore, an effective approach to studying the mechanism and development of outburst is to conduct the similar physical simulation. However, the similarity criteria and similar materials in outburst are the key factors which restrict the development of physical simulation. To solve those problems, this paper has established similarity criteria base on mechanics model, solid-fluid coupling model and energy model, and presented high similar materials. Combining with three groups of similar number, and considering similar mechanical parameters and deformation and failure regularity, the similarity criteria of outburst is determined on the basis of the energy model. According to those criteria, we put forward a similar material consists of pulverized coal, cement, sand, activated carbon, and water. The similar material has high compressive strength and the accordant characteristics with the raw coal, include density, porosity, adsorption, desorption. The new research is promising for preventing and controlling gas hazards in the future.展开更多
Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the...Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.展开更多
An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were ran...An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were randomly divided into 2 treatments for 8 weeks (16 replicates/group and 1 rabbit/replicate). The treatments were fed a basal diet (control, measured pyridoxine content is 4.51 mg/kg) and the basal diet with a pyridoxine supplementation at 10 mg/kg (pyridoxine, measured pyridoxine content is 14.64 mg/kg). The results showed that dietary pyridoxine did not significantly alter the mRNA levels of neuropeptide Y, agouti related peptide, pro-opiomelanocortin and cocaine, amphetamine regulated transcript, peptide YY and cholecystokinin in arcuate nucleus, peptide YY in jejunum and ileum, and cholecystokinin in duodenum, jejunum and ileum (P > 0.05). Compared with the control, the mRNA levels of corticotropin-releasing hormone and melanocortin 4 receptor in paraventricular nuclei and peptide YY in duodenum were significantly decreased after pyridoxine treatment (P 0.05). In conclusion, the appetite genes of melanocortin 4 receptor and corticotropin-releasing hormone in paraventricular nuclei and peptide YY in duodenum are involved in the pyridoxine-caused hyperphagia.展开更多
Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is a common metabolic liver disease worldwide.Currently,satisfactory drugs for NAFLD treatment remain lacking.Obesity and diabetes are the le...Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is a common metabolic liver disease worldwide.Currently,satisfactory drugs for NAFLD treatment remain lacking.Obesity and diabetes are the leading causes of NAFLD,and compounds with anti-obesity and antidiabetic activities are considered suitable candidates for treating NAFLD.In this study,biochemical and histological assays revealed that a natural lignan schisanhenol(SAL)effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid(FFA)-treated HepG2 cells and high-fat diet(HFD)-induced NAFLD mice.Further,molecular analyses,microRNA(miRNA)-seq,and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphateactivated protein kinase(AMPK)pathway.Liver-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated(p)-AMPK and PRKAB1.Dual-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3’untranslated region of mouse Prkab1 or human PRKAA1.展开更多
Background:Colon cancer is one of the most prevalent digestive cancers worldwide.Results of epidemiological,experimental,and clinical studies suggest that aspirin inhibits the development of colon cancer.This study ai...Background:Colon cancer is one of the most prevalent digestive cancers worldwide.Results of epidemiological,experimental,and clinical studies suggest that aspirin inhibits the development of colon cancer.This study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon carcinogenesis.Methods:We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic analysis.We analyzed the proteomic results using bioinformatics(including differential pro-teins,protein annotation,Kyoto Encyclopedia of Genes and Genomes[KEGG]pathways,and protein-protein inter-action[PPI]network).The viability of the colon cancer cell line and HT29 cells treated with aspirin was determined using the cell counting kit-8 assay.The differentially expressed proteins,such as p53 and cyclin-dependent kinase 1(CDK1),were quantified using real-time polymerase chain reaction(PCR)and Western blotting.We measured cell cycle distribution and apoptosis in HT29 cells exposed to aspirin using fluorescence-activated cell sorting(FACS).Results:We found that 552 proteins were significantly dysregulated,of which 208 and 334 were upregulated and downregulated,respectively,in colon cancer cells exposed to 10 mmol/L of aspirin(95%confidence interval[CI]:-1.269 to-0.106,P<0.05).Further gene enrichment analysis revealed that cell cycle-related proteins,such as p53 and CDK1,were significantly differentially expressed.Proteomic analysis showed that after 24 h of aspirin exposure,the level of p53 increased by 2.52-fold and CDK1 was downregulated to half that of the controls in HT29 cells(95%CI:-0.619 to-0.364,P<0.05).Real-time PCR and Western blotting results showed that p53 was upregulated(95%CI:-3.088 to-1.912,P<0.001)and CDK1 was significantly downregulated after aspirin exposure in colon cancer cells(95%CI:0.576 to 1.045,P<0.05).We observed that aspirin promoted G1/S cell cycle arrest in HT29 cells.We confirmed that aspirin induces apoptosis in human HT29 colon cancer cells in a concentration-dependent manner.Conclusions:These results indicate that aspirin induces G1 arrest and apoptosis in colorectal cancer cells via the p53-CDK1 pathway.Aspirin may be a promising drug candidate for colon cancer prevention.展开更多
Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes.They widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining g...Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes.They widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material.Through cellular evolution of prokaryotic to eukaryotic,nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates,including flaps,bubbles,and Holliday junctions.These special structural configurations are commonly found as intermediates in processes like DNA replication,repair,and recombination.The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells.In this article,we review their roles in various pathways,including Okazaki fragment maturation during DNA replication,end resection in homology-directed recombination repair of DNA double-strand breaks,DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage,and HIV life cycle.As the nucleases serve as key points for the DNA dynamics,cellular apoptosis,and cancer cell survival pathways,we discuss the efforts in the field in developing the therapeutic regimens,taking advantage of recently available knowledge of their diversified structures and functions.展开更多
This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5...This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0,5,10,20,or 40 mg/kg pyridoxine.The hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase(PI3 K)/protein kinase B(PKB or Akt),Wnt,Notch and bone morphogenetic protein(BMP)signalling pathways were measured.In addition,free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft growth.Furthermore,dermal papilla cells(DPC)were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3 K/Akt,Wnt,Notch and BMP signalling pathways.The results showed that the addition of dietary pyridoxine significantly increased the total follicle density,secondary follicle density,and secondary-to-primary ratio(S/P,P<0.05),that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium,and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group(P<0.05).In addition,pyridoxine changed the DPC cycle progression and promoted cell proliferation,and appropriate concentrations of pyridoxine(10 and 20μmol/L)significantly inhibited cell apoptosis(P<0.05).Pyridoxine significantly affected the gene expression of components of the PI3 K/Akt,Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits(P<0.05),increased the levels of phosphorylated catenin beta 1(CTNNB1)and Akt,and decreased the level of phosphorylated glycogen synthase kinase 3 beta(GSK-3β)(P<0.05).Therefore,the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3 K/Akt,Wnt and Notch signalling pathways,prolonging hair follicle growth and delaying the onset of telogen.展开更多
Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically us...Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.展开更多
The second near-infrared(NIR-II,1,000 to 1,700 nm)molecular fluorophores containing donor–acceptor–donor conjugated backbone have attracted substantial attention due to their outstanding advantages,such as stable em...The second near-infrared(NIR-II,1,000 to 1,700 nm)molecular fluorophores containing donor–acceptor–donor conjugated backbone have attracted substantial attention due to their outstanding advantages,such as stable emission and facilely tuned photophysical properties.However,it is still challenging for them to simultaneously achieve high brightness and red-shifted absorption and emission.Herein,furan is adopted as the D unit to construct NIR-II fluorophores,demonstrating red shift of absorption,enhanced absorption coefficient,and fluorescent quantum yield when compared with the generally used thiophene counterparts.The high brightness and desirable pharmacokinetics of the optimized fluorophore,IR-FFCHP,endows improved performance for angiography and tumor-targeting imaging.Furthermore,dual-NIR-II imaging of tumor and sentinel lymph nodes(LNs)has been achieved with IR-FFCHP and PbS/CdS quantum dots,enabling the in vivo imaging navigated LN surgery in tumor-bearing mice.This work demonstrates the potential of furan for constructing bright NIR-II fluorophores for biological imaging.展开更多
Resistive random access memory(RRAM) has been considered as one of the most promising candidates for next-generation nonvolatile memory, due to its advantages of simple device structure, excellent scalability, fast op...Resistive random access memory(RRAM) has been considered as one of the most promising candidates for next-generation nonvolatile memory, due to its advantages of simple device structure, excellent scalability, fast operation speed and low power consumption. Deeply understanding the physical mechanism and effectively controlling the statistical variation of switching parameters are the basis of fostering RRAM into commercial application. In this paper, based on the deep understanding on the mechanism of the formation and rupture of conductive filament, we summarize the methods of analyzing and modeling the statistics of switching parameters such as SET/RESET voltage, current, speed or time. Then, we analyze the distributions of switching parameters and the influencing factors. Additionally, we also sum up the analytical model of resistive switching statistics composed of the cell-based percolation model and SET/RESET switching dynamics. The results of the model can successfully explain the experimental distributions of switching parameters of the Ni O- and Hf O2-based RRAM devices. The model also provides theoretical guide on how to improve the uniformity and reliability such as disturb immunity. Finally, some experimental approaches to improve the uniformity of switching parameters are discussed.展开更多
It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report ...It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report a molecular engineering approach to afford NIR-Ⅱ fluorophores with these merits based on fused-ring acceptor(FRA)molecules.Dioctyl 3,4-propylenedioxy thiophene(PDOT-C8)is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene(3-EHOT),leading to more than 20 times enhancement of brightness.The nanofluorophores(NFs)based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield(QY)of 0.39%(QY of IR-26 is 0.050%in dichloroethane as reference)and peak absorption coefficient of 14.5 x 10^4 M^-1·cm^-1 in aqueous solutions,which are significantly higher than those of 3-EHOT based COTIC-4F NFs.It is found that PDOT-C8 can weaken intermolecular aggregation,enhance protection of molecular backbone from water,and decrease backbone distortion,beneficial for the high brightness.Compared with indocyanine green with same injection dose,CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.展开更多
The fabrication of highly effective photosensitizers has received considerable attention because of their attractive functions and applications in the fields of photodynamic therapy, photosynthesis, photocatalysis, et...The fabrication of highly effective photosensitizers has received considerable attention because of their attractive functions and applications in the fields of photodynamic therapy, photosynthesis, photocatalysis, etc. Thus, it is highly desirable to develop a new approach to enhance photosensitization efficiency.Herein, through coordination-driven self-assembly, a series of metallacycles with efficient fluorescence resonance energy transfer(FRET) were effectively constructed, which displayed higher photosensitization efficiency and photocatalytic activity than their model metallacycles without FRET due to broadband absorption and singlet energy transfer from the energy acceptor to the energy donor. Moreover, iodization of fluorophores induced a significant enhancement of the photosensitization efficiency and photocatalytic activity of the metallacycles. This research provides an efficient strategy for improving photosensitization efficiency and a promising platform for the preparation of effective photosensitizers and photocatalysts.展开更多
A series of triphe nylamine(TPA)derivatives with various substituent groups were prepared and showed different absorption and fluorescence characteristics due to the substituent effect.On account of the existence of p...A series of triphe nylamine(TPA)derivatives with various substituent groups were prepared and showed different absorption and fluorescence characteristics due to the substituent effect.On account of the existence of pyridine units,these TPA derivatives exhibited acid-induced tunable multicolor fluorescence emission including white light emission.In addition,acid-induced fluorescence regulation of these compounds has been also realized in the solid state,which enable them to be successfully constructed the stimuli-responsive fluorescent films and fluorescent inks for inkjet printing.展开更多
Thermally activated delayed fluorescence(TADF) emitters are primarily comprised of intramolecular charge-transfer(ICT) molecules with small energy difference between the lowest singlet and triplet excited states.T...Thermally activated delayed fluorescence(TADF) emitters are primarily comprised of intramolecular charge-transfer(ICT) molecules with small energy difference between the lowest singlet and triplet excited states.They lend extremely favorable electroluminescent performance to organic light-emitting diodes(OLEDs).This paper summarizes relevant issues and research efforts in the theoretical prediction of singlet- and triplet-transition energies of ICT molecules via time-dependent density functional theory(TDDFT).The successful application of the descriptor-based optimal Hartree-Fock percentage method and the optimally tuned range-separated functional to many TADF systems represent an interesting approach to the exact prediction of the complex excited-state molecular dynamics within TDDFT.展开更多
基金Acknowledgements This work was financially supported by the National Key Research and Development Program (2016YFC0801402-4), the National Natural Science Foundation of China (51374236, 51574280), Chongqing Frontiers and Application- based Research Program (cstc2015jcyjBX0076). Meanwhile, the author would like to thank the reviewers of this paper for their constructive comments and suggestions to improve the publication.
文摘Coal and gas outburst is one of the main gas hazards in coal mines. However, due to the risks of the coal and gas outburst, the field test is difficult to complete. Therefore, an effective approach to studying the mechanism and development of outburst is to conduct the similar physical simulation. However, the similarity criteria and similar materials in outburst are the key factors which restrict the development of physical simulation. To solve those problems, this paper has established similarity criteria base on mechanics model, solid-fluid coupling model and energy model, and presented high similar materials. Combining with three groups of similar number, and considering similar mechanical parameters and deformation and failure regularity, the similarity criteria of outburst is determined on the basis of the energy model. According to those criteria, we put forward a similar material consists of pulverized coal, cement, sand, activated carbon, and water. The similar material has high compressive strength and the accordant characteristics with the raw coal, include density, porosity, adsorption, desorption. The new research is promising for preventing and controlling gas hazards in the future.
基金National Natural Science Foundation of China(Nos.31970663 and 82173028 to J.X.,No.81874180 to T.W.,No.81201556 to W.Z.,No.82072971 to H.W.and No.81972505 to Z.W.)。
文摘Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.
文摘An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were randomly divided into 2 treatments for 8 weeks (16 replicates/group and 1 rabbit/replicate). The treatments were fed a basal diet (control, measured pyridoxine content is 4.51 mg/kg) and the basal diet with a pyridoxine supplementation at 10 mg/kg (pyridoxine, measured pyridoxine content is 14.64 mg/kg). The results showed that dietary pyridoxine did not significantly alter the mRNA levels of neuropeptide Y, agouti related peptide, pro-opiomelanocortin and cocaine, amphetamine regulated transcript, peptide YY and cholecystokinin in arcuate nucleus, peptide YY in jejunum and ileum, and cholecystokinin in duodenum, jejunum and ileum (P > 0.05). Compared with the control, the mRNA levels of corticotropin-releasing hormone and melanocortin 4 receptor in paraventricular nuclei and peptide YY in duodenum were significantly decreased after pyridoxine treatment (P 0.05). In conclusion, the appetite genes of melanocortin 4 receptor and corticotropin-releasing hormone in paraventricular nuclei and peptide YY in duodenum are involved in the pyridoxine-caused hyperphagia.
基金National Natural Science Foundation of China(Nos.82304708 and U23A20511)the CAMS Innovation Fund for Medical Sciences(2023-I2M-QJ-013,2021-I2M-1-031,2022-I2M-2-002,and 2023-I2M-3-006,China)the Beijing Natural Science Foundation(No.Z220019,China).
文摘Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is a common metabolic liver disease worldwide.Currently,satisfactory drugs for NAFLD treatment remain lacking.Obesity and diabetes are the leading causes of NAFLD,and compounds with anti-obesity and antidiabetic activities are considered suitable candidates for treating NAFLD.In this study,biochemical and histological assays revealed that a natural lignan schisanhenol(SAL)effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid(FFA)-treated HepG2 cells and high-fat diet(HFD)-induced NAFLD mice.Further,molecular analyses,microRNA(miRNA)-seq,and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphateactivated protein kinase(AMPK)pathway.Liver-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated(p)-AMPK and PRKAB1.Dual-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3’untranslated region of mouse Prkab1 or human PRKAA1.
基金supported by the Science and Technology Plan of Beijing Tongzhou District(Nos.KJ2019CX012-38 and KJ2020CX006-11)the Youth Research and Development Fund of Beijing Luhe Hospital,Capital Medical University(No.LHYY2020-JC10).
文摘Background:Colon cancer is one of the most prevalent digestive cancers worldwide.Results of epidemiological,experimental,and clinical studies suggest that aspirin inhibits the development of colon cancer.This study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon carcinogenesis.Methods:We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic analysis.We analyzed the proteomic results using bioinformatics(including differential pro-teins,protein annotation,Kyoto Encyclopedia of Genes and Genomes[KEGG]pathways,and protein-protein inter-action[PPI]network).The viability of the colon cancer cell line and HT29 cells treated with aspirin was determined using the cell counting kit-8 assay.The differentially expressed proteins,such as p53 and cyclin-dependent kinase 1(CDK1),were quantified using real-time polymerase chain reaction(PCR)and Western blotting.We measured cell cycle distribution and apoptosis in HT29 cells exposed to aspirin using fluorescence-activated cell sorting(FACS).Results:We found that 552 proteins were significantly dysregulated,of which 208 and 334 were upregulated and downregulated,respectively,in colon cancer cells exposed to 10 mmol/L of aspirin(95%confidence interval[CI]:-1.269 to-0.106,P<0.05).Further gene enrichment analysis revealed that cell cycle-related proteins,such as p53 and CDK1,were significantly differentially expressed.Proteomic analysis showed that after 24 h of aspirin exposure,the level of p53 increased by 2.52-fold and CDK1 was downregulated to half that of the controls in HT29 cells(95%CI:-0.619 to-0.364,P<0.05).Real-time PCR and Western blotting results showed that p53 was upregulated(95%CI:-3.088 to-1.912,P<0.001)and CDK1 was significantly downregulated after aspirin exposure in colon cancer cells(95%CI:0.576 to 1.045,P<0.05).We observed that aspirin promoted G1/S cell cycle arrest in HT29 cells.We confirmed that aspirin induces apoptosis in human HT29 colon cancer cells in a concentration-dependent manner.Conclusions:These results indicate that aspirin induces G1 arrest and apoptosis in colorectal cancer cells via the p53-CDK1 pathway.Aspirin may be a promising drug candidate for colon cancer prevention.
基金This work was supported by National Institutes of Health(NIH)/National Cancer Institute(NCI)grants(R01CA073764,R01CA085344,and R01CA233664 to B.S.and R50CA211397 to L.Z.)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS,2023-I2M-3-006 to H.S.).
文摘Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes.They widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material.Through cellular evolution of prokaryotic to eukaryotic,nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates,including flaps,bubbles,and Holliday junctions.These special structural configurations are commonly found as intermediates in processes like DNA replication,repair,and recombination.The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells.In this article,we review their roles in various pathways,including Okazaki fragment maturation during DNA replication,end resection in homology-directed recombination repair of DNA double-strand breaks,DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage,and HIV life cycle.As the nucleases serve as key points for the DNA dynamics,cellular apoptosis,and cancer cell survival pathways,we discuss the efforts in the field in developing the therapeutic regimens,taking advantage of recently available knowledge of their diversified structures and functions.
基金supported by the National Natural Science Foundation of China(31972594)Earmarked Fund for Modern Agro-industry Technology Research System(CARS-43-B-1)+2 种基金the Thoroughbred Project from Shandong Government(2017LZN008)Shandong Province Modern Agricultural Technology System Innovation Team(SDAIT-21)Funds of Shandong“Double Tops”Programme(SYL2017YSTD11)。
文摘This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0,5,10,20,or 40 mg/kg pyridoxine.The hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase(PI3 K)/protein kinase B(PKB or Akt),Wnt,Notch and bone morphogenetic protein(BMP)signalling pathways were measured.In addition,free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft growth.Furthermore,dermal papilla cells(DPC)were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3 K/Akt,Wnt,Notch and BMP signalling pathways.The results showed that the addition of dietary pyridoxine significantly increased the total follicle density,secondary follicle density,and secondary-to-primary ratio(S/P,P<0.05),that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium,and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group(P<0.05).In addition,pyridoxine changed the DPC cycle progression and promoted cell proliferation,and appropriate concentrations of pyridoxine(10 and 20μmol/L)significantly inhibited cell apoptosis(P<0.05).Pyridoxine significantly affected the gene expression of components of the PI3 K/Akt,Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits(P<0.05),increased the levels of phosphorylated catenin beta 1(CTNNB1)and Akt,and decreased the level of phosphorylated glycogen synthase kinase 3 beta(GSK-3β)(P<0.05).Therefore,the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3 K/Akt,Wnt and Notch signalling pathways,prolonging hair follicle growth and delaying the onset of telogen.
基金supported by National Natural Science Foundation of China(Grants 21878088,12034008,21476077,11727810)Key projects of Shanghai Science and Technology Commission(18DZ1112703)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,grant 2021 Sci&Tech 03-28)。
文摘Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.
基金the National Natural Science Foundation of China(Nos.21772084 and 12034008)Fundamental Research Layout of Shenzhen(No.JCY20180504165657443)+3 种基金Guangdong Provincial Natural Science Foundation-Yueshen Joint Funding(Youth Project)(No.2019A1515110464)the Shenzhen Science and Technology Commission-free exploration/general project(No.JCYJ20190812151209348)Special fund for local science and technology development guided by central government is acknowledged.The support from Shanghai Rising Star Program(No.21QA1402600)the graduate fellowship(201808440345)from Chinese Scholarship Council are also acknowledged.
文摘The second near-infrared(NIR-II,1,000 to 1,700 nm)molecular fluorophores containing donor–acceptor–donor conjugated backbone have attracted substantial attention due to their outstanding advantages,such as stable emission and facilely tuned photophysical properties.However,it is still challenging for them to simultaneously achieve high brightness and red-shifted absorption and emission.Herein,furan is adopted as the D unit to construct NIR-II fluorophores,demonstrating red shift of absorption,enhanced absorption coefficient,and fluorescent quantum yield when compared with the generally used thiophene counterparts.The high brightness and desirable pharmacokinetics of the optimized fluorophore,IR-FFCHP,endows improved performance for angiography and tumor-targeting imaging.Furthermore,dual-NIR-II imaging of tumor and sentinel lymph nodes(LNs)has been achieved with IR-FFCHP and PbS/CdS quantum dots,enabling the in vivo imaging navigated LN surgery in tumor-bearing mice.This work demonstrates the potential of furan for constructing bright NIR-II fluorophores for biological imaging.
基金supported by the National Natural Science Foundation of China(61322408,61221004,61334007,61274091,61106119 and 61106082)National Basic Research Program of China(2010CB934200 and 2011CBA00602)National High Technology Research and Development Program of China(2011AA010401 and 2011AA010402)
文摘Resistive random access memory(RRAM) has been considered as one of the most promising candidates for next-generation nonvolatile memory, due to its advantages of simple device structure, excellent scalability, fast operation speed and low power consumption. Deeply understanding the physical mechanism and effectively controlling the statistical variation of switching parameters are the basis of fostering RRAM into commercial application. In this paper, based on the deep understanding on the mechanism of the formation and rupture of conductive filament, we summarize the methods of analyzing and modeling the statistics of switching parameters such as SET/RESET voltage, current, speed or time. Then, we analyze the distributions of switching parameters and the influencing factors. Additionally, we also sum up the analytical model of resistive switching statistics composed of the cell-based percolation model and SET/RESET switching dynamics. The results of the model can successfully explain the experimental distributions of switching parameters of the Ni O- and Hf O2-based RRAM devices. The model also provides theoretical guide on how to improve the uniformity and reliability such as disturb immunity. Finally, some experimental approaches to improve the uniformity of switching parameters are discussed.
基金supported by the National Natural Science Foundation of China(52172223,52272230,and 51972223)the Young Elite Scientists Sponsorship Program by Tianjin(TJSQNTJ-202011)+3 种基金the National Key Research and Development Program of China(2021YFF0500600 and 2022YFB2404500)the National IndustryEducation Integration Platform of Energy Storagethe Haihe Laboratory of Sustainable Chemical Transformationsthe Fundamental Research Funds for the Central Universities。
基金Y.L.acknowledges financial supports from the National Natural Science Foundation of China(No.21772084)Fundamental Research Layout of Shenzhen(No.JCY20180504165657443)+2 种基金H.S.thanks the National Natural Science Foundation of China(Nos.11727810,61720106009 and 21603074)the Science and Technology Commission of Shanghai Municipality(No.19JC1412200)for funding support and the ECNU Multifunctional Platform for Innovation(001)and HPC Research Computing Team for providing computational and storage resourcesX.Z thanks the funding supports from the National Natural Science Foundation of China(Nos.91859101,81971744,and U1932107).
文摘It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report a molecular engineering approach to afford NIR-Ⅱ fluorophores with these merits based on fused-ring acceptor(FRA)molecules.Dioctyl 3,4-propylenedioxy thiophene(PDOT-C8)is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene(3-EHOT),leading to more than 20 times enhancement of brightness.The nanofluorophores(NFs)based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield(QY)of 0.39%(QY of IR-26 is 0.050%in dichloroethane as reference)and peak absorption coefficient of 14.5 x 10^4 M^-1·cm^-1 in aqueous solutions,which are significantly higher than those of 3-EHOT based COTIC-4F NFs.It is found that PDOT-C8 can weaken intermolecular aggregation,enhance protection of molecular backbone from water,and decrease backbone distortion,beneficial for the high brightness.Compared with indocyanine green with same injection dose,CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.
基金supported by the National Nature Science Foundation of China (No. 21871092)Program of Shanghai Outstanding Academic Leaders (No. 21XD1421200)+1 种基金the Fundamental Research Funds for the Central Universities2021 Academic Innovation Ability Enhancement Plan for Excellent Doctoral Students of East China Normal University (No. YBNLTS2021-025)。
文摘The fabrication of highly effective photosensitizers has received considerable attention because of their attractive functions and applications in the fields of photodynamic therapy, photosynthesis, photocatalysis, etc. Thus, it is highly desirable to develop a new approach to enhance photosensitization efficiency.Herein, through coordination-driven self-assembly, a series of metallacycles with efficient fluorescence resonance energy transfer(FRET) were effectively constructed, which displayed higher photosensitization efficiency and photocatalytic activity than their model metallacycles without FRET due to broadband absorption and singlet energy transfer from the energy acceptor to the energy donor. Moreover, iodization of fluorophores induced a significant enhancement of the photosensitization efficiency and photocatalytic activity of the metallacycles. This research provides an efficient strategy for improving photosensitization efficiency and a promising platform for the preparation of effective photosensitizers and photocatalysts.
基金supported by the State Key Laboratory of Fine Chemicals(No.KF1801)。
文摘A series of triphe nylamine(TPA)derivatives with various substituent groups were prepared and showed different absorption and fluorescence characteristics due to the substituent effect.On account of the existence of pyridine units,these TPA derivatives exhibited acid-induced tunable multicolor fluorescence emission including white light emission.In addition,acid-induced fluorescence regulation of these compounds has been also realized in the solid state,which enable them to be successfully constructed the stimuli-responsive fluorescent films and fluorescent inks for inkjet printing.
基金the Exploratory Research for Advanced Technology (ERATO) of Japanthe Key Special Program of the Ministry of Science and Technology of China(No.2016YFB0401000) for financial support
文摘Thermally activated delayed fluorescence(TADF) emitters are primarily comprised of intramolecular charge-transfer(ICT) molecules with small energy difference between the lowest singlet and triplet excited states.They lend extremely favorable electroluminescent performance to organic light-emitting diodes(OLEDs).This paper summarizes relevant issues and research efforts in the theoretical prediction of singlet- and triplet-transition energies of ICT molecules via time-dependent density functional theory(TDDFT).The successful application of the descriptor-based optimal Hartree-Fock percentage method and the optimally tuned range-separated functional to many TADF systems represent an interesting approach to the exact prediction of the complex excited-state molecular dynamics within TDDFT.