Background Wool fibers are valuable materials for textile industry.Typical wool fibers are divided into medullated and non-medullated types,with the former generated from primary wool follicles and the latter by eithe...Background Wool fibers are valuable materials for textile industry.Typical wool fibers are divided into medullated and non-medullated types,with the former generated from primary wool follicles and the latter by either primary or secondary wool follicles.The medullated wool is a common wool type in the ancestors of fine wool sheep before breeding.The fine wool sheep have a non-medullated coat.However,the critical period determining the type of wool follicles is the embryonic stage,which limits the phenotypic observation and variant contrast,making both selection and studies of wool type variation fairly difficult.Results During the breeding of a modern fine(MF)wool sheep population with multiple-ovulation and embryo transfer technique,we serendipitously discovered lambs with ancestral-like coarse(ALC)wool.Whole-genome rese-quencing confirmed ALC wool lambs as a variant type from the MF wool population.We mapped the significantly associated methylation locus on chromosome 4 by using whole genome bisulfite sequencing signals,and in turn identified the SOSTDC1 gene as exons hypermethylated in ALC wool lambs compare to their half/full sibling MF wool lambs.Transcriptome sequencing found that SOSTDC1 was expressed dozens of times more in ALC wool lamb skin than that of MF and was at the top of all differentially expressed genes.An analogy with the transcriptome of coarse/fine wool breeds revealed that differentially expressed genes and enriched pathways at postnatal lamb stage in ALC/MF were highly similar to those at the embryonic stage in the former.Further experiments validated that the SOSTDC1 gene was specifically highly expressed in the nucleus of the dermal papilla of primary wool follicles.Conclusion In this study,we conducted genome-wide differential methylation site association analysis on differen-tial wool type trait,and located the only CpG locus that strongly associated with primary wool follicle development.Combined with transcriptome analysis,SOSTDC1 was identified as the only gene at this locus that was specifically overexpressed in the primary wool follicle stem cells of ALC wool lamb skin.The discovery of this key gene and its epigenetic regulation contributes to understanding the domestication and breeding of fine wool sheep.展开更多
Here,this work presents an air-stable ultrabright inverted organic lightemitting device(OLED)by using zinc ionchelated polyethylenimine(PEI)as electron injection layer.The zinc chelation is demonstrated to increase th...Here,this work presents an air-stable ultrabright inverted organic lightemitting device(OLED)by using zinc ionchelated polyethylenimine(PEI)as electron injection layer.The zinc chelation is demonstrated to increase the conductivity of the PEI by three orders of magnitude and passivate the polar amine groups.With these physicochemical properties,the inverted OLED shows a record-high external quantum efficiency of 10.0% at a high brightness of 45,610 cd m^(-2) and can deliver a maximum brightness of 121,865 cd m^(-2).Besides,the inverted OLED is also demonstrated to possess an excellent air stability(humidity,35%)with a half-brightness operating time of 541 h@1000 cd m^(-2) without any protection nor encapsulation.展开更多
Influenza viruses are major respiratory pathogens known to infect human and a variety of animals and are widely prevalent worldwide.Genome structure of influenza D virus(IDV)is identical to that of influenza C virus(I...Influenza viruses are major respiratory pathogens known to infect human and a variety of animals and are widely prevalent worldwide.Genome structure of influenza D virus(IDV)is identical to that of influenza C virus(ICV),and phylogenetic analyses suggest that IDV and ICV share a common ancestry and high homology.To date,the prevalence of ICV and IDV in China is unclear,but these viruses represent a potential threat to public health due to cross-species transmission and zoonotic potential.To efficiently monitor ICV and IDV,it is necessary to establish a dual detection method to understand their prevalence and conduct in-depth research.A duplex real-time PCR method for the simultaneous detection of ICV and IDV was developed.TaqMan fluorescent probes and specific primers targeting NP gene of ICV and PB1 gene of IDV were designed.This method exhibited good specificity and sensitivity,and the detection limit reached 1 × 10^(1) copies/pL of plasmid standards of each pathogen.Thirty-one clinical swine samples and 10 clinical cattle samples were analyzed using this method.One positive sample of IDV was detected,and the accuracy of clinical test results was verified by conventional PCR and DNA sequencing.The duplex real-time PCR detection method represents a sensitive and specific tool to detect IG/and IDV,It provides technical support for virus research and clinical diagnosis of ICV and IDV.This information will benefit animal and human health.展开更多
A novel and sustainable visible-light-enabled multicomponent reaction involving quinoxalin-2(1H)-ones,indoles,and CF3SO2Na that does not require an external photocatalyst is described.This photoinduced reaction employ...A novel and sustainable visible-light-enabled multicomponent reaction involving quinoxalin-2(1H)-ones,indoles,and CF3SO2Na that does not require an external photocatalyst is described.This photoinduced reaction employs air as the sole oxidant,thereby providing a green and highly step-efficient approach to a series of biologically important trifluoromethylated 3-indolequinoxalin-2(1H)-ones.展开更多
Top-illuminated structure facilitates the integration of organic photodetectors(OPDs)into high-resolution flexible wearable light detection systems by allowing the OPDs to be deposited on the bottom readout circuit.Ho...Top-illuminated structure facilitates the integration of organic photodetectors(OPDs)into high-resolution flexible wearable light detection systems by allowing the OPDs to be deposited on the bottom readout circuit.However,constructing this structure poses a challenge as it demands metallic electrodes with both high optical transparency and high electrical conductivity.But to achieve practical sheet resistances,most semitransparent metallic electrodes tend to reflect a large portion of incident light instead of allowing it to be absorbed by the photoactive layer of the OPDs.This,in turn,results in reduced photocurrent generation.To address this issue,a semiconducting germanium(Ge)film is introduced into a sliver(Ag)film,effectively reducing its reflectivity by lessening scattering.The Ge film also changes how the Ag film grows,further reducing its absorption by lowering the critical thickness needed for forming a continuous film.This approach yields a 10 nm metallic electrode with a transmittance of 70%,a reflectivity of 12%,and a sheet resistance of 35.5Ω/□.Using this metallic electrode,flexible OPDs exhibit a high photo-to-dark current ratio of 2.9×10^(4)and improved mechanical properties.This finding highlights the benefits of the top-illuminated structure,which effectively reduces losses caused by waveguided modes of the incident light.展开更多
Resonance interaction between a molecular transition and a confined electromagnetic field can lead to weak or strong light-matter coupling.Considering the substantial exciton–phonon coupling in thermally activated de...Resonance interaction between a molecular transition and a confined electromagnetic field can lead to weak or strong light-matter coupling.Considering the substantial exciton–phonon coupling in thermally activated delayed fluorescence(TADF)materials,it is thus interesting to explore whether weak light-matter coupling can be used to redistribute optical density of states and to change the rate of radiative decay.Here,we demonstrate that the emission distribution of TADF emitters can be reshaped and narrowed in a top-emitting organic light-emitting device(OLED)with a weakly coupled microcavity.The Purcell effect of weak microcavity is found to be different for TADF emitters with different molecular orientations.We demonstrate that radiative rates of the TADF emitters with vertical orientation can be substantial increased in weakly coupled organic microcavity.These observations can enhance external quantum efficiencies,reduce efficiency roll-off,and improve color-purities of TADF OLEDs,especially for emitters without highly horizontal orientation.展开更多
As a primary anticounterfeiting technology,most paper anticounterfeiting devices take advantage of photoresponsive behaviors of certain security materials or structures,thus featuring low-security threshold,which has ...As a primary anticounterfeiting technology,most paper anticounterfeiting devices take advantage of photoresponsive behaviors of certain security materials or structures,thus featuring low-security threshold,which has been a critical global issue.To incorporate optoelectronic devices into existing anticounterfeiting technology suggests a feasible avenue to address this challenge.Here we report a high-performance organic light-emitting paper-based flexible anticounterfeiting(FAC)device with multiple stimuli-responsiveness,including light,electricity,and their combination.Without sacrificing the preexisted security information on the paper,we fabricate FAC device in a facile,low-cost yet high-fidelity fashion by integrating patterned electro-responsive and photo-responsive organic emitters onto paper substrates.By introducing optical microcavities,the FAC device shows considerable color shift upon different viewing angle and applied voltage,which is easily discernible by naked eyes.Notably,the FAC device is bendable,unclonable,and durable(a half-lifetime over 4000 hours at 100 cd m^(−2)).展开更多
A novel synthesis of 2,3-dihydroimidazo[1,2-a]pyridin-5 (1H)-one 4 and its derivatives were described.Preliminary bioassays showed that some of the target compounds exhibited excellent insecticidal activities against ...A novel synthesis of 2,3-dihydroimidazo[1,2-a]pyridin-5 (1H)-one 4 and its derivatives were described.Preliminary bioassays showed that some of the target compounds exhibited excellent insecticidal activities against brown planthopper (Nilaparvata lugens), cowpea aphids (Aphis craccivora) (4,5 a, 5 c, 5 g,5 h, 5 j, 5 r, 6 b, 6 e) and carmine spider mite (Tetranychus cinnabarinus (5 f, 5 s, 6 a) at 500 mg/L. Among them,compound 4 was still active against brown planthopper and cowpea aphids at 4 mg/L. The insecticidal activities were influenced by the types and position of the substituents, which provided guidance for the structure modifications.展开更多
Epithelial ovarian cancer(EOC)is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC.Although the loss of 4.1N is associated with i...Epithelial ovarian cancer(EOC)is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC.Although the loss of 4.1N is associated with increased risk of malignancy,its association with EOC remains unclear.To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition(EMT)and matrixdetached cell death resistance,we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays.We report that the loss of 4.1N correlated with progress in clinical stage,as well as poor survival in EOC patients.The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells.Furthermore,the loss of 4.1N could increase the rate of entosis,which aggravates cell death resistance in suspension EOC cells.Moreover,xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells.Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees.Our results not only define the vital role of 4.1N loss in inducing EMT,anoikis resistance,and entosis-induced cell death resistance in EOC,but also suggest that individual or combined application of 4.1N,14-3-3 antagonists,and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.展开更多
This paper will first carry out experimental investigations on a test compressor which is a large-scale,two-stage and low-speed axial one to evaluate the participation of a novel casing treatment(stall precursor-suppr...This paper will first carry out experimental investigations on a test compressor which is a large-scale,two-stage and low-speed axial one to evaluate the participation of a novel casing treatment(stall precursor-suppressed casing treatment,SPS CT).The compressor performance for its pressure rise characteristics and efficiency are tested and illustrated.Besides,the time-averaged steady and the time-resolved unsteady measurement in this paper finally lead to some further analyses about the stall evolution of this compressor tending to uncover the process of the stall evolution and the mechanism of the SPS CT.The overall performance results indicate that the SPS CT can extend the compressor stall margin by 3%e11%with very limited efficiency loss.And the mechanism for such casing treatment has also been revealed as stall-precursor suppression by observing the evolution of the inception waves.In addition,modeling work have been conducted subject to the effects of SPS CT on the test two-stage axial compressor.The compressor stability model is able to investigate the effects of different geometrical parameters on the compressor stability and then make an optimal design for the SPS CT when it is applied on the test compressor.展开更多
Human dihydroorotate dehydrogenase(DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis(RA), psoriasis and multiple sclerosis(MS). Here...Human dihydroorotate dehydrogenase(DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis(RA), psoriasis and multiple sclerosis(MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog 11 was identified as the lead compound for structureeactivity relationship(SAR) studies. The replacement of the phenyl group with naphthyl moieties improved inhibitory activity significantly to double-digit nanomolar range.Further structure optimization revealed that an acrylamide with small hydrophobic groups(Me, Cl or Br)at the 2-position was preferred. Moreover, adding a fluoro atom at the 5-position of the benzoic acid enhanced the potency. The optimization efforts led to potent compounds 42 and 53-55 with IC50 values of 41, 44, 32, and 42 nmol/L, respectively. The most potent compound 54 also displayed favorable pharmacokinetic(PK) profiles and encouraging in vivo anti-arthritic effects in a dose-dependent manner.展开更多
The development of organic materials with white-light emission and thermally activated delayed fluorescence(TADF)properties in the solid state remain a challenge.Herein,a series of white-light-emitting organic luminog...The development of organic materials with white-light emission and thermally activated delayed fluorescence(TADF)properties in the solid state remain a challenge.Herein,a series of white-light-emitting organic luminogens have been developed and are found to show aggregation-induced delayed fluorescence(AIDF)characteristics.The AIDF emitters present dual-emission consisted of prompt fluorescence and TADF in the crystalline state.Their white-light emissions can be easily tuned by altering the chemical structure and connecting position of the heterocyclic aromatic substituent.Under the stimuli of mechanical force and solvent vapor,the compounds exhibit remarkable and reversible mechanochromism,in which their emission colors are switchable between white and yellow.Upon grinding,they also display linearly tunable luminescence colors,as well as force-induced TADF enhancement,which may be associated with the more compact molecular packing and the restriction of intramolecular motions.The results from time-resolved emission scanning and theoretical calculation suggest that the dual-emission of the AIDF luminogens likely results from the twisted intramolecular charge transfer transitions of the molecules,and the reversible mechanochromism properties probably stem from the interconversion of the quasi-axial and the quasi-equatorial conformations.展开更多
基金the programs of National Key R&D Program of China(2021YFF1000700)National Natural Science Foundation of China(32002145)+1 种基金the Major Project for Cultivation Technology of New Varieties of Genetically Modified Organisms of the Ministry of Agriculture(grant Nos.2016ZX08008-001 and 2013ZX08008-001)Ningxia Agricultural Breeding Project(NXNYYZ2015010).
文摘Background Wool fibers are valuable materials for textile industry.Typical wool fibers are divided into medullated and non-medullated types,with the former generated from primary wool follicles and the latter by either primary or secondary wool follicles.The medullated wool is a common wool type in the ancestors of fine wool sheep before breeding.The fine wool sheep have a non-medullated coat.However,the critical period determining the type of wool follicles is the embryonic stage,which limits the phenotypic observation and variant contrast,making both selection and studies of wool type variation fairly difficult.Results During the breeding of a modern fine(MF)wool sheep population with multiple-ovulation and embryo transfer technique,we serendipitously discovered lambs with ancestral-like coarse(ALC)wool.Whole-genome rese-quencing confirmed ALC wool lambs as a variant type from the MF wool population.We mapped the significantly associated methylation locus on chromosome 4 by using whole genome bisulfite sequencing signals,and in turn identified the SOSTDC1 gene as exons hypermethylated in ALC wool lambs compare to their half/full sibling MF wool lambs.Transcriptome sequencing found that SOSTDC1 was expressed dozens of times more in ALC wool lamb skin than that of MF and was at the top of all differentially expressed genes.An analogy with the transcriptome of coarse/fine wool breeds revealed that differentially expressed genes and enriched pathways at postnatal lamb stage in ALC/MF were highly similar to those at the embryonic stage in the former.Further experiments validated that the SOSTDC1 gene was specifically highly expressed in the nucleus of the dermal papilla of primary wool follicles.Conclusion In this study,we conducted genome-wide differential methylation site association analysis on differen-tial wool type trait,and located the only CpG locus that strongly associated with primary wool follicle development.Combined with transcriptome analysis,SOSTDC1 was identified as the only gene at this locus that was specifically overexpressed in the primary wool follicle stem cells of ALC wool lamb skin.The discovery of this key gene and its epigenetic regulation contributes to understanding the domestication and breeding of fine wool sheep.
基金supported by the National Natural Science Foundation of China(Grant Nos.61905086,62174067,62175085)Science and Technology Development Planning of Jilin Province(Project Nos.20190101024JH,20200201296JC)+1 种基金the Hong Kong Scholars Program(Project No.XJ2020028)grants from the Research Grants Council of the Hong Kong Special Administrative Region,China(Project Nos.11300418 and 11300419).
文摘Here,this work presents an air-stable ultrabright inverted organic lightemitting device(OLED)by using zinc ionchelated polyethylenimine(PEI)as electron injection layer.The zinc chelation is demonstrated to increase the conductivity of the PEI by three orders of magnitude and passivate the polar amine groups.With these physicochemical properties,the inverted OLED shows a record-high external quantum efficiency of 10.0% at a high brightness of 45,610 cd m^(-2) and can deliver a maximum brightness of 121,865 cd m^(-2).Besides,the inverted OLED is also demonstrated to possess an excellent air stability(humidity,35%)with a half-brightness operating time of 541 h@1000 cd m^(-2) without any protection nor encapsulation.
基金This work was financially supported by the National Key Research and Development Program of China(2017YFD0500101)the Fundamental Research Funds for the Central Universities(Y0201900459).
文摘Influenza viruses are major respiratory pathogens known to infect human and a variety of animals and are widely prevalent worldwide.Genome structure of influenza D virus(IDV)is identical to that of influenza C virus(ICV),and phylogenetic analyses suggest that IDV and ICV share a common ancestry and high homology.To date,the prevalence of ICV and IDV in China is unclear,but these viruses represent a potential threat to public health due to cross-species transmission and zoonotic potential.To efficiently monitor ICV and IDV,it is necessary to establish a dual detection method to understand their prevalence and conduct in-depth research.A duplex real-time PCR method for the simultaneous detection of ICV and IDV was developed.TaqMan fluorescent probes and specific primers targeting NP gene of ICV and PB1 gene of IDV were designed.This method exhibited good specificity and sensitivity,and the detection limit reached 1 × 10^(1) copies/pL of plasmid standards of each pathogen.Thirty-one clinical swine samples and 10 clinical cattle samples were analyzed using this method.One positive sample of IDV was detected,and the accuracy of clinical test results was verified by conventional PCR and DNA sequencing.The duplex real-time PCR detection method represents a sensitive and specific tool to detect IG/and IDV,It provides technical support for virus research and clinical diagnosis of ICV and IDV.This information will benefit animal and human health.
基金This work was supported by Basic Scientific Research Special Funds(No.2020XZ011)Zhejiang Shuren University,the"Ten-thousand Talents Plan"of Zhejiang Province(No.2019R51012)+1 种基金the Technology Research and Development Program of Hangzhou(No.20191203B28)the National Natural Science Foundation of China(No.21302171).
文摘A novel and sustainable visible-light-enabled multicomponent reaction involving quinoxalin-2(1H)-ones,indoles,and CF3SO2Na that does not require an external photocatalyst is described.This photoinduced reaction employs air as the sole oxidant,thereby providing a green and highly step-efficient approach to a series of biologically important trifluoromethylated 3-indolequinoxalin-2(1H)-ones.
基金National Natural Science Foundation of China(62174067,62175085,62374071)Science and Technology Development Planning of Jilin Province(20230101061JC)。
文摘Top-illuminated structure facilitates the integration of organic photodetectors(OPDs)into high-resolution flexible wearable light detection systems by allowing the OPDs to be deposited on the bottom readout circuit.However,constructing this structure poses a challenge as it demands metallic electrodes with both high optical transparency and high electrical conductivity.But to achieve practical sheet resistances,most semitransparent metallic electrodes tend to reflect a large portion of incident light instead of allowing it to be absorbed by the photoactive layer of the OPDs.This,in turn,results in reduced photocurrent generation.To address this issue,a semiconducting germanium(Ge)film is introduced into a sliver(Ag)film,effectively reducing its reflectivity by lessening scattering.The Ge film also changes how the Ag film grows,further reducing its absorption by lowering the critical thickness needed for forming a continuous film.This approach yields a 10 nm metallic electrode with a transmittance of 70%,a reflectivity of 12%,and a sheet resistance of 35.5Ω/□.Using this metallic electrode,flexible OPDs exhibit a high photo-to-dark current ratio of 2.9×10^(4)and improved mechanical properties.This finding highlights the benefits of the top-illuminated structure,which effectively reduces losses caused by waveguided modes of the incident light.
基金supported by the National Natural Science Foundation of China(grant nos.61774074 and 61905086)Science and Technology Development Planning of Jilin Province(project nos.20190101024JH and 20200201296JC)+1 种基金the Hong Kong Scholars Program(project no.XJ2020028)grants from the Research Grants Council of the Hong Kong Special Administrative Region,China(project nos.11300418 and 11300419).
文摘Resonance interaction between a molecular transition and a confined electromagnetic field can lead to weak or strong light-matter coupling.Considering the substantial exciton–phonon coupling in thermally activated delayed fluorescence(TADF)materials,it is thus interesting to explore whether weak light-matter coupling can be used to redistribute optical density of states and to change the rate of radiative decay.Here,we demonstrate that the emission distribution of TADF emitters can be reshaped and narrowed in a top-emitting organic light-emitting device(OLED)with a weakly coupled microcavity.The Purcell effect of weak microcavity is found to be different for TADF emitters with different molecular orientations.We demonstrate that radiative rates of the TADF emitters with vertical orientation can be substantial increased in weakly coupled organic microcavity.These observations can enhance external quantum efficiencies,reduce efficiency roll-off,and improve color-purities of TADF OLEDs,especially for emitters without highly horizontal orientation.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.62175085,62174067,and 61905086)Science and Technology Development Planning of Jilin Province(Project No.20200201296JC)the Hong Kong Scholars Program(Project No.XJ2020028).
文摘As a primary anticounterfeiting technology,most paper anticounterfeiting devices take advantage of photoresponsive behaviors of certain security materials or structures,thus featuring low-security threshold,which has been a critical global issue.To incorporate optoelectronic devices into existing anticounterfeiting technology suggests a feasible avenue to address this challenge.Here we report a high-performance organic light-emitting paper-based flexible anticounterfeiting(FAC)device with multiple stimuli-responsiveness,including light,electricity,and their combination.Without sacrificing the preexisted security information on the paper,we fabricate FAC device in a facile,low-cost yet high-fidelity fashion by integrating patterned electro-responsive and photo-responsive organic emitters onto paper substrates.By introducing optical microcavities,the FAC device shows considerable color shift upon different viewing angle and applied voltage,which is easily discernible by naked eyes.Notably,the FAC device is bendable,unclonable,and durable(a half-lifetime over 4000 hours at 100 cd m^(−2)).
基金financial supported by the National Key Research Program of China(No. 2017YFD0200500)National Natural Science Foundation of China(No.21672061)supported by the Fundamental Research Funds for the Central Universities(No. 222201718004)
文摘A novel synthesis of 2,3-dihydroimidazo[1,2-a]pyridin-5 (1H)-one 4 and its derivatives were described.Preliminary bioassays showed that some of the target compounds exhibited excellent insecticidal activities against brown planthopper (Nilaparvata lugens), cowpea aphids (Aphis craccivora) (4,5 a, 5 c, 5 g,5 h, 5 j, 5 r, 6 b, 6 e) and carmine spider mite (Tetranychus cinnabarinus (5 f, 5 s, 6 a) at 500 mg/L. Among them,compound 4 was still active against brown planthopper and cowpea aphids at 4 mg/L. The insecticidal activities were influenced by the types and position of the substituents, which provided guidance for the structure modifications.
基金This work was supported by grants from National Key Research and Development Program of China(2018YFC1004002)the National Natural Science Foundation of China(No.81472430 and 81672457)the Clinical Medicine Plus X-Young Scholars Project of Peking University(PKU2019LCXQ01).
文摘Epithelial ovarian cancer(EOC)is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC.Although the loss of 4.1N is associated with increased risk of malignancy,its association with EOC remains unclear.To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition(EMT)and matrixdetached cell death resistance,we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays.We report that the loss of 4.1N correlated with progress in clinical stage,as well as poor survival in EOC patients.The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells.Furthermore,the loss of 4.1N could increase the rate of entosis,which aggravates cell death resistance in suspension EOC cells.Moreover,xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells.Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees.Our results not only define the vital role of 4.1N loss in inducing EMT,anoikis resistance,and entosis-induced cell death resistance in EOC,but also suggest that individual or combined application of 4.1N,14-3-3 antagonists,and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.
基金the National Natural Science Foundation of China(Nos.51906004,51822601 and 5156008)National Science and Technology Major Project(2017-II-0005-0018).
文摘This paper will first carry out experimental investigations on a test compressor which is a large-scale,two-stage and low-speed axial one to evaluate the participation of a novel casing treatment(stall precursor-suppressed casing treatment,SPS CT).The compressor performance for its pressure rise characteristics and efficiency are tested and illustrated.Besides,the time-averaged steady and the time-resolved unsteady measurement in this paper finally lead to some further analyses about the stall evolution of this compressor tending to uncover the process of the stall evolution and the mechanism of the SPS CT.The overall performance results indicate that the SPS CT can extend the compressor stall margin by 3%e11%with very limited efficiency loss.And the mechanism for such casing treatment has also been revealed as stall-precursor suppression by observing the evolution of the inception waves.In addition,modeling work have been conducted subject to the effects of SPS CT on the test two-stage axial compressor.The compressor stability model is able to investigate the effects of different geometrical parameters on the compressor stability and then make an optimal design for the SPS CT when it is applied on the test compressor.
基金supported by the National Key Research and Development Program (2017YFD0200505 to Xiaoyong Xu,2016YFA0502304 to Honglin Li, China)the National Natural Science Foundation of China (81825020 to Honglin Li, 81803437to Shiliang Li)+5 种基金the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(2018ZX09711002, China)the Fundamental Research Funds for the Central Universitiesthe Shanghai Foundation of Science and Technology (15431902100 to Xiaoyong Xu)sponsored by Shanghai Sailing Program (No. 18YF1405100,China)sponsored by the National Program for Special Supports of Eminent ProfessionalsNational Program for Support of Top-Notch Young Professionals,China。
文摘Human dihydroorotate dehydrogenase(DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis(RA), psoriasis and multiple sclerosis(MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog 11 was identified as the lead compound for structureeactivity relationship(SAR) studies. The replacement of the phenyl group with naphthyl moieties improved inhibitory activity significantly to double-digit nanomolar range.Further structure optimization revealed that an acrylamide with small hydrophobic groups(Me, Cl or Br)at the 2-position was preferred. Moreover, adding a fluoro atom at the 5-position of the benzoic acid enhanced the potency. The optimization efforts led to potent compounds 42 and 53-55 with IC50 values of 41, 44, 32, and 42 nmol/L, respectively. The most potent compound 54 also displayed favorable pharmacokinetic(PK) profiles and encouraging in vivo anti-arthritic effects in a dose-dependent manner.
基金supported by the National Natural Science Foundation of China(No.51603233)the Natural Science Foundation of Guangdong Province of China(Nos.2019A1515010550,2020A1515010439,2019A1515011389)the GDUPS(2019)the Opening Foundation of Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education(Sun Yat-sen University,No.PCFM-2019-05)。
文摘The development of organic materials with white-light emission and thermally activated delayed fluorescence(TADF)properties in the solid state remain a challenge.Herein,a series of white-light-emitting organic luminogens have been developed and are found to show aggregation-induced delayed fluorescence(AIDF)characteristics.The AIDF emitters present dual-emission consisted of prompt fluorescence and TADF in the crystalline state.Their white-light emissions can be easily tuned by altering the chemical structure and connecting position of the heterocyclic aromatic substituent.Under the stimuli of mechanical force and solvent vapor,the compounds exhibit remarkable and reversible mechanochromism,in which their emission colors are switchable between white and yellow.Upon grinding,they also display linearly tunable luminescence colors,as well as force-induced TADF enhancement,which may be associated with the more compact molecular packing and the restriction of intramolecular motions.The results from time-resolved emission scanning and theoretical calculation suggest that the dual-emission of the AIDF luminogens likely results from the twisted intramolecular charge transfer transitions of the molecules,and the reversible mechanochromism properties probably stem from the interconversion of the quasi-axial and the quasi-equatorial conformations.