With the innovation of microelectronics technology, the heat dissipation problem inside the device will face a severe test. In this work, cellulose aerogel(CA) with highly enhanced thermal conductivity(TC) in vertical...With the innovation of microelectronics technology, the heat dissipation problem inside the device will face a severe test. In this work, cellulose aerogel(CA) with highly enhanced thermal conductivity(TC) in vertical planes was successfully obtained by constructing a vertically aligned silicon carbide nanowires(SiC NWs)/boron nitride(BN) network via the ice template-assisted strategy. The unique network structure of SiC NWs connected to BN ensures that the TC of the composite in the vertical direction reaches 2.21 W m^(-1) K^(-1) at a low hybrid filler loading of 16.69 wt%, which was increased by 890% compared to pure epoxy(EP). In addition, relying on unique porous network structure of CA, EP-based composite also showed higher TC than other comparative samples in the horizontal direction. Meanwhile, the composite exhibits good electrically insulating with a volume electrical resistivity about 2.35 × 10^(11) Ω cm and displays excellent electromagnetic wave absorption performance with a minimum reflection loss of-21.5 dB and a wide effective absorption bandwidth(<-10 dB) from 8.8 to 11.6 GHz. Therefore, this work provides a new strategy for manufacturing polymer-based composites with excellent multifunctional performances in microelectronic packaging applications.展开更多
The scaled-up synthesis of organic-free monolayer nanomaterials is highly desirable,especially in obtaining green energy by electrocatalysis.In this study,a method for the scaled-up synthesis of the series of monolaye...The scaled-up synthesis of organic-free monolayer nanomaterials is highly desirable,especially in obtaining green energy by electrocatalysis.In this study,a method for the scaled-up synthesis of the series of monolayer layered double hydroxides(LDHs)without the addition of organic solvents is reported via the separate nucleation and aging steps process.The resulting monolayer LDHs with the thicknesses of less than 1 nm showed a narrow thickness distribution.X-ray absorption fine-structure revealed that monolayer NiFe-LDH nanosheets have a number of oxygen and metal vacancies defects.As a practical application,monolayer NiFe-LDH nanosheets containing defects showed an enhanced electrocatalytic water oxidation activity compared with that of bulk NiFe-LDH.Density functional theory calculations uncovered that excellent catalytic activity is attributed to vacancies defects.The proposed method is an economical and universally applicable strategy for the scaled-up production of monolayer LDHs.展开更多
Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors.Although degradation of fiber is a promising strategy,its application was still bottlenecked by the side effects of causing metastas...Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors.Although degradation of fiber is a promising strategy,its application was still bottlenecked by the side effects of causing metastasis,resulting in the failure of immunotherapy.Here,we developed an antimetastatic polymer(HPA)for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator.Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis,and further promoted the sustained infiltration and activation of T cells for killing tumor cells.Moreover,metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs.The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+T cells to 52.5%in tumor tissues,inhibiting nearly 90%metastasis by HPA in distant organs.The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.展开更多
Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have ...Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.展开更多
With the discovery of the two-dimensional(2D) MXene, it shows a great application potential in the field of electromagnetic interference(EMI) shielding, but the mechanical brittleness and easy oxidation of MXene limit...With the discovery of the two-dimensional(2D) MXene, it shows a great application potential in the field of electromagnetic interference(EMI) shielding, but the mechanical brittleness and easy oxidation of MXene limit its wide application. For this reason, a double crosslinking strategy is provided to solve the above problems in a nacre-like “brick-mortar” layered MXene/cellulose nanofiber(MXene/CNF) film.Typically, the film was firstly suffered by dopamine modification, then was further reinforced by secondary Ca^(2+)bridging, so as to obtain excellent mechanical properties and antioxidative EMI shielding performance. Comparing with the single crosslinking, the double crosslinking strategy reveals a higher efficiency in improving the mechanical property. The mechanical strength and toughness of the double crosslinking MXene/CNF film can increase to 142.2 MPa and 9.48 MJ/m^(3), respectively. More importantly, while achieving good mechanical properties, the MXene composite film still holds a very stable EMI shielding performance of more than 44.6 dB when suffering from the oxidation treatment of hightemperature annealing, showing excellent anti-oxidation ability and environment tolerance. Therefore,this work provides a universal but effective double crosslinking strategy to solve the mechanical brittleness and easy oxidation of MXene-based composites, thus showing a huge potential in flexible EMI shielding applications.展开更多
Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an a...Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity.Using flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 level.TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1.Furthermore,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity.Mechanistically,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent pathway.TBM-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome biogenesis.Moreover,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)cells.Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.展开更多
This study was to examine the sedative–hypnotic effect of YZG-330 and its influence on Cl−influx in mouse cortical cells.In a sleep time-prolongation test in which mice were administered a threshold dosage of sodium ...This study was to examine the sedative–hypnotic effect of YZG-330 and its influence on Cl−influx in mouse cortical cells.In a sleep time-prolongation test in which mice were administered a threshold dosage of sodium pentobarbital(ip),YZG-330(0.125,0.5 and 2 mg/kg,po)prolonged the sleep time by 25%(P40.05),64%(Po0.01)and 506%(Po0.001),respectively.Thereafter,treatment with YZG-330 permitted mice that had woken up after the threshold dose of sodium pentobarbital(ip)to fall asleep again.A Cl−-sensitive fluorescent probe,N-(ethoxycarbonylmethyl)-methoxyquinolinium bromide(MQAE),was used to determine the effect of YZG-330 on Cl−influx.YZG-330(0.3,0.6 and 1.5 mM)increased Cl−influx in mouse cortical cells in a concentration-dependent manner.These data suggest that YZG-330 has a hypnotic effect in mice,and the effect may be related to an increase in Cl−influx in cortical cells.展开更多
Three-dimensional(3D)imaging radar is an advanced sensor applied in space surveillance and target recognition for supplying 3D geometric features and supporting visualization.However,high 3D resolution requires both b...Three-dimensional(3D)imaging radar is an advanced sensor applied in space surveillance and target recognition for supplying 3D geometric features and supporting visualization.However,high 3D resolution requires both broadband operation and a large 2D aperture,which are difficult and complex for conventional radars.This paper presents a photonics-enabled distributed multiple-input and multiple-output(MIMO)radar with a centralized architecture.By use of photonic multi-dimensional multiplexing,multi-channel signal generation and reception are implemented on a shared reference signal in a central office,enabling a highly coherent network with a simple structure.Additionally,a sparse array and a synthetic aperture are combined to efficiently reduce the required transceivers,further weakening the dilemma between system complexity and angular resolution.A 4×4 MIMO radar is established and evaluated in field tests.A high-resolution 3D image of a non-cooperative aircraft is obtained,in which rich details are displayed.From a comparison with electronics-based radar,significant resolution improvement is observed.The results verify the superior imaging capability and practicability of the proposed radar and its great potential to outperform conventional technologies in target classification and recognition applications.展开更多
基金financial support from National Natural Science Foundation of China(21704096,51703217)the China Postdoctoral Science Foundation(Grant No.2019M662526)financial support from Taif University Researchers Supporting Project Number(TURSP-2020/135),Taif University,Taif,Saudi Arabia。
文摘With the innovation of microelectronics technology, the heat dissipation problem inside the device will face a severe test. In this work, cellulose aerogel(CA) with highly enhanced thermal conductivity(TC) in vertical planes was successfully obtained by constructing a vertically aligned silicon carbide nanowires(SiC NWs)/boron nitride(BN) network via the ice template-assisted strategy. The unique network structure of SiC NWs connected to BN ensures that the TC of the composite in the vertical direction reaches 2.21 W m^(-1) K^(-1) at a low hybrid filler loading of 16.69 wt%, which was increased by 890% compared to pure epoxy(EP). In addition, relying on unique porous network structure of CA, EP-based composite also showed higher TC than other comparative samples in the horizontal direction. Meanwhile, the composite exhibits good electrically insulating with a volume electrical resistivity about 2.35 × 10^(11) Ω cm and displays excellent electromagnetic wave absorption performance with a minimum reflection loss of-21.5 dB and a wide effective absorption bandwidth(<-10 dB) from 8.8 to 11.6 GHz. Therefore, this work provides a new strategy for manufacturing polymer-based composites with excellent multifunctional performances in microelectronic packaging applications.
基金supported by the National Nature Science Foundation of China(U1707603,21878008,21625101,U1507102,21922801)the Beijing Natural Science Foundation(2182047,2202036)the Fundamental Research Funds for the Central Universities(XK1802-6,XK1902,12060093063,2312018RC07)。
文摘The scaled-up synthesis of organic-free monolayer nanomaterials is highly desirable,especially in obtaining green energy by electrocatalysis.In this study,a method for the scaled-up synthesis of the series of monolayer layered double hydroxides(LDHs)without the addition of organic solvents is reported via the separate nucleation and aging steps process.The resulting monolayer LDHs with the thicknesses of less than 1 nm showed a narrow thickness distribution.X-ray absorption fine-structure revealed that monolayer NiFe-LDH nanosheets have a number of oxygen and metal vacancies defects.As a practical application,monolayer NiFe-LDH nanosheets containing defects showed an enhanced electrocatalytic water oxidation activity compared with that of bulk NiFe-LDH.Density functional theory calculations uncovered that excellent catalytic activity is attributed to vacancies defects.The proposed method is an economical and universally applicable strategy for the scaled-up production of monolayer LDHs.
基金financially supported by the National Key Research and Development Program of China(2017YFA0205402)the National Natural Science Foundation of China(81872817,82102202)+1 种基金Natural Science Foundation of Jiangsu Province(BK20210424,China)the Postdoctoral Innovative Talent Support Program(BX20200387,China)。
文摘Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors.Although degradation of fiber is a promising strategy,its application was still bottlenecked by the side effects of causing metastasis,resulting in the failure of immunotherapy.Here,we developed an antimetastatic polymer(HPA)for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator.Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis,and further promoted the sustained infiltration and activation of T cells for killing tumor cells.Moreover,metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs.The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+T cells to 52.5%in tumor tissues,inhibiting nearly 90%metastasis by HPA in distant organs.The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.
基金supported by grants from National Natural Science Foundation of China(81973366,81773782 and 81903695)CAMS Innovation Fund for Medical Sciences(2016-12M-1-011,China)+2 种基金Open Project of State Key Laboratory of Bioactive Substance and Function of Natural Medicines(GTZK201908,China)National Mega-project for Innovative Drugs(2019ZX09721-001,China)Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund for Biomedicine(GL-1-B04-20180366,China)
文摘Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.
基金financially supported by the National Key R&D Program of China(No.2019YFA0706802)the National Natural Science Foundation of China(Nos.51903223 and 12072325)the Key Technologies R&D Program of Henan Province(No.212102210302)。
文摘With the discovery of the two-dimensional(2D) MXene, it shows a great application potential in the field of electromagnetic interference(EMI) shielding, but the mechanical brittleness and easy oxidation of MXene limit its wide application. For this reason, a double crosslinking strategy is provided to solve the above problems in a nacre-like “brick-mortar” layered MXene/cellulose nanofiber(MXene/CNF) film.Typically, the film was firstly suffered by dopamine modification, then was further reinforced by secondary Ca^(2+)bridging, so as to obtain excellent mechanical properties and antioxidative EMI shielding performance. Comparing with the single crosslinking, the double crosslinking strategy reveals a higher efficiency in improving the mechanical property. The mechanical strength and toughness of the double crosslinking MXene/CNF film can increase to 142.2 MPa and 9.48 MJ/m^(3), respectively. More importantly, while achieving good mechanical properties, the MXene composite film still holds a very stable EMI shielding performance of more than 44.6 dB when suffering from the oxidation treatment of hightemperature annealing, showing excellent anti-oxidation ability and environment tolerance. Therefore,this work provides a universal but effective double crosslinking strategy to solve the mechanical brittleness and easy oxidation of MXene-based composites, thus showing a huge potential in flexible EMI shielding applications.
基金supported by grants from National Natural Science Foundation of China(81973366,81773782,81903695 and 82003792)CAMS Innovation Fund for Medical Sciences(2016I2M-1-011,China)+1 种基金National Mega-project for Innovative Drugs(2019ZX09721-001,China)Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund for Biomedicine(GL-1-B04-20180366,China)。
文摘Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity.Using flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 level.TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1.Furthermore,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity.Mechanistically,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent pathway.TBM-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome biogenesis.Moreover,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)cells.Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.
基金from National S&T Major Special Project on Major New Drug Innovation(Item Number:2012ZX09103-101-001)the National Natural Science Foundation(No.81202521).
文摘This study was to examine the sedative–hypnotic effect of YZG-330 and its influence on Cl−influx in mouse cortical cells.In a sleep time-prolongation test in which mice were administered a threshold dosage of sodium pentobarbital(ip),YZG-330(0.125,0.5 and 2 mg/kg,po)prolonged the sleep time by 25%(P40.05),64%(Po0.01)and 506%(Po0.001),respectively.Thereafter,treatment with YZG-330 permitted mice that had woken up after the threshold dose of sodium pentobarbital(ip)to fall asleep again.A Cl−-sensitive fluorescent probe,N-(ethoxycarbonylmethyl)-methoxyquinolinium bromide(MQAE),was used to determine the effect of YZG-330 on Cl−influx.YZG-330(0.3,0.6 and 1.5 mM)increased Cl−influx in mouse cortical cells in a concentration-dependent manner.These data suggest that YZG-330 has a hypnotic effect in mice,and the effect may be related to an increase in Cl−influx in cortical cells.
基金National Natural Science Foundation of China(61690191,62101536)。
文摘Three-dimensional(3D)imaging radar is an advanced sensor applied in space surveillance and target recognition for supplying 3D geometric features and supporting visualization.However,high 3D resolution requires both broadband operation and a large 2D aperture,which are difficult and complex for conventional radars.This paper presents a photonics-enabled distributed multiple-input and multiple-output(MIMO)radar with a centralized architecture.By use of photonic multi-dimensional multiplexing,multi-channel signal generation and reception are implemented on a shared reference signal in a central office,enabling a highly coherent network with a simple structure.Additionally,a sparse array and a synthetic aperture are combined to efficiently reduce the required transceivers,further weakening the dilemma between system complexity and angular resolution.A 4×4 MIMO radar is established and evaluated in field tests.A high-resolution 3D image of a non-cooperative aircraft is obtained,in which rich details are displayed.From a comparison with electronics-based radar,significant resolution improvement is observed.The results verify the superior imaging capability and practicability of the proposed radar and its great potential to outperform conventional technologies in target classification and recognition applications.