This study investigates the effects of cold-acclimation in conferring chilling tolerance in seedlings of the mulberry(Morus alba) variety ‘Qiuyu’. Changes in photosynthesis and antioxidant enzymes in chilling acclim...This study investigates the effects of cold-acclimation in conferring chilling tolerance in seedlings of the mulberry(Morus alba) variety ‘Qiuyu’. Changes in photosynthesis and antioxidant enzymes in chilling acclimatized(CA), and non-acclimatized(NA) seedlings were recorded during chilling stress(3 °C) and a recovery period(25 °C) each for 3 days. The results showed that CA plants had higher net photosynthetic rates(P_n), stomatal conductance(G_s), and maximum photochemical efficiency of photosystem Ⅱ(F_v/F_m) in response to chilling stress compared to NA. The seedlings maintained the same trends during the recovery stage. The responses of Q_A reduction degree (1-q_P) and prime electronic transfer rates(F_o) were lower in acclimatized than in non-acclimatized seedlings. Low-temperature acclimation and chilling stress also caused an increase in leaf proline and soluble sugar contents. Leaf malondialdehyde levels were significantly lower while ascorbate peroxidase(APX) activity was significantly higher in acclimatized seedlings, suggesting that elevated osmolytes and APX confer resistance to chilling temperatures. In this study on the response of mulberry seedlings to chilling stress, we also looked at the recovery process. The response to chilling determines whether mulberry leaves can survive under cold temperatures, while the recovery process determines whether photosynthesis can recover as soon as possible to avoid any secondary damage.展开更多
Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid peroxidation.However,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent...Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid peroxidation.However,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis.Herein,a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin(DOX),iron and unsaturated lipid for efficient ferroptosis.By leveraging the coordination effect between DOX and Fe3+,trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method.First,Fe3+could react with the overexpressed GSH in tumor cells,inducing the GSH depletion and Fe2+generation.Second,the cleavage of trisulfide bond could also consume GSH,and the released DOX induces the generation of H2O2,which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis.Third,the formed Fe3+/Fe2+couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis.This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion,ROS generation and lipid peroxidation,providing new sights for efficient cancer therapy.展开更多
It is significant for identifying mass movement patterns to invert horizontal tectonic stresses at different depths underneath Tibet.In recent years,a large number of achievements focusing on two-dimensional tectonic ...It is significant for identifying mass movement patterns to invert horizontal tectonic stresses at different depths underneath Tibet.In recent years,a large number of achievements focusing on two-dimensional tectonic stresses have been obtained from gravity data.However,three-dimensional tectonic stresses in Tibet are still unknown or debatable.Therefore,in the present study an improved method to multilayer horizontal tectonic stresses using gravity observations is developed.The inverted multilayer horizontal tectonic stresses are in agreement with those from previous studies.In addition,rich tectonic structure and development can be revealed from the inverted multilayer horizontal tectonic stresses:(1)the distribution of horizontal tectonic stresses at various depths shows strong correlation with that of the tectonic elements,where major faults and earthquake epicenters are corresponding with stress highs and the stable basins are consistent with stress lows.(2)the mass movement patterns of whole Tibet present clockwise,and the material movement directions in the west and east are approximately southnorth and east-west,respectively.(3)in eastern Tibet,the eastward materials caused by the south-north extrusion between Indian and Eurasian plates are divided into two parts by the stable Sichuan Block,one flowing nearly southeast and the other moving almost northeast.The inverted multilayer horizontal tectonic stresses may provide direct evidences for mass movement patterns in Tibet.展开更多
The solution culture method was used to study the effect of increasing nitrogen on the growth and pho-tosynthesis of poplar seedlings under 100 mmol L-1 NaCl stress. I Increase in nitrogen reduced stomatal limitation ...The solution culture method was used to study the effect of increasing nitrogen on the growth and pho-tosynthesis of poplar seedlings under 100 mmol L-1 NaCl stress. I Increase in nitrogen reduced stomatal limitation of leaves under NaCl stress, improved utilization of CO2 by mesophyll cells, enhanced photosynthetic carbon assimi-lation capacity, significantly alleviated saline damage of NaCl, and promoted the accumulation of aboveground and root biomass. I Increased nitrogen enhanced photochemical efficiency (ΦPSⅡ) and electron transport rates, relieved the reduction of maximum photochemical efficiency (Fv/Fm) under NaCl, and reduced the degree of photoinhibition caused by NaCl stress. Increased nitrogen applications reduced the proportion of energy dissipating in the form of ineffective heat energy and hence a greater proportion of light energy absorbed by leaves was allocated to photo-chemical reactions. Under treatment with increased nitro-gen, the synergistic effect of heat dissipation and the xanthophyll cycle in the leaves effectively protected pho-tosynthetic PSⅡ and enhanced light energy utilization of leaves under NaCl stress. The increased nitrogen promoted photosynthetic electron supply and transport ability under NaCl stress evident in enhanced functioning of the oxygen-evolving complex on the electron donor side of PS Ⅱ. It increased the ability of the receptor pool to accept electrons on the PSII electron acceptor side and improved the sta-bility of thylakoid membranes under NaCl stress. Therefore, increasing nitrogen applications under NaCl stress can promote poplar growth by improving the effi-ciency of light energy utilization.展开更多
To construct pulsed high magnet, with rapid adjustments to large changes in the field strength, it is a mandatory acces-sory to development a special NMR probes to provide a precise real-time map of the magnetic field...To construct pulsed high magnet, with rapid adjustments to large changes in the field strength, it is a mandatory acces-sory to development a special NMR probes to provide a precise real-time map of the magnetic field. In order to do so, it is necessary to understand the variations of the spin transition and susceptibility of NMR samples in a time dependent longitudinal field. This work analyzes the effect on the spin transition by a time dependent longitudinal field. For a 1/2 spin system, we have derived a simple formula for the prediction of the probabilities of occupation of the 1/2 and ?1/2 states in a non-static field. We also calculate the magnetic susceptibility of the water and give an analysis of the effect on the magnetic susceptibility in a time dependent longitudinal field and RF frequency.展开更多
In recent years,through financial subsidies,Shouguang City has promoted the application of electrostatic sprayer,dual-purpose fog and mist sprinkler machine,Bacillus cereus,flame disinfection service based on fine rot...In recent years,through financial subsidies,Shouguang City has promoted the application of electrostatic sprayer,dual-purpose fog and mist sprinkler machine,Bacillus cereus,flame disinfection service based on fine rotary tillage and multi-functional plant protection machine and other new green prevention and control products and technologies for the greenhouse vegetable in the city. As a result,the utilization rate of pesticides was increased by more than 5%,and the application rate was reduced by more than 10%.展开更多
The aim of the present study was to determine whether the sensitivity of thymocytes to X-ray radiation depends on their proliferative states and whether radiation impairs the maturation of donor-derived thymocytes in ...The aim of the present study was to determine whether the sensitivity of thymocytes to X-ray radiation depends on their proliferative states and whether radiation impairs the maturation of donor-derived thymocytes in recipient thymus.We assigned 8-week-old C57BL/6J mice into three treatment groups:1) untreated;2) X-ray radiation;3) X-ray radiation plus bone marrow transplantation with donor bone marrow cells from transgenic mice express-ing enhanced green fluorescent protein(GFP) on a universal promoter.After 4 weeks,the size of the thymus,the number and proliferation of thymocytes and ratios of different stage thymocytes were analyzed by immunohisto-chemistry and flow cytometry.The results showed that:1) CD4+CD8+ thymocytes were more sensitive to X-ray radiation-induced cell death than other thymocytes;2) the proliferative capacity of CD4+CD8+ thymocytes was higher than that of other thymocytes;3) the size of the thymus,the number of thymocytes and ratios of thymo-cytes of different stages in irradiated mice recovered to the normal level of untreated mice by bone marrow trans-plantation;4) the ratio of GFP-positive CD4+CD8+ thymocytes increased significantly,whereas the ratio of GFP-positive CD4+ or CD8+ thymocytes decreased significantly.These results indicate that the degree of sensitivity of thymocytes to X-ray radiation depends on their proliferative states and radiation impairs the maturation of donor-derived CD4+CD8+ thymocytes in recipient thymus.展开更多
Lithium-sulfur(Li-S)batteries have been regarded as the candidate for the next-generation energy storage system due to the high theoretical specific capacity(1675 m Ah/g), energy density(2600 Wh/kg)and the abundance o...Lithium-sulfur(Li-S)batteries have been regarded as the candidate for the next-generation energy storage system due to the high theoretical specific capacity(1675 m Ah/g), energy density(2600 Wh/kg)and the abundance of elemental sulfur, but the application of Li-S batteries is impeded by a series of problems. Recently, all-solid-state Li-S batteries(ASSLSBs) have drawn great attention because many drawbacks such as safety issues caused by metallic lithium anodes and organic liquid electrolytes can be overcome through the use of solid-state electrolytes(SEs). However, not only the problems brought by sulfur cathodes still exist, but more trouble arouses from the interfaces between SEs and cathodes, hampering the practical application of ASSLSBs. Therefore, in order to deal with the problems, enormous endeavors have been done on ASSLSB cathodes during the past few decades, including engineering of cathode active materials, cathode host materials, cathode binder materials and cathode structures. In this review, the electrochemical mechanism and existing problems of ASSLSBs are briefly introduced. Subsequently, the strategies for developing cathode materials and designing cathode structures are presented. Then there follows a brief discussion of SE problems and expectations, and finally, the challenges and perspectives of ASSLSBs are summarized.展开更多
Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it ha...Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.展开更多
The combination of paclitaxel(PTX)and doxorubicin(DOX)has been widely used in the clinic.However,it remains unsatisfied due to the generation of severe toxicity.Previously,we have successfully synthesized a prodrug PT...The combination of paclitaxel(PTX)and doxorubicin(DOX)has been widely used in the clinic.However,it remains unsatisfied due to the generation of severe toxicity.Previously,we have successfully synthesized a prodrug PTX-S-DOX(PSD).The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX.Thus,we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation.Due to the fact that copper ions(Cu2+)could coordinate with the anthracene nucleus of DOX,we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+gradient.Hence,we designed a remote loading liposomal formulation of PSD(PSD LPs)for combination chemotherapy.The prepared PSD LPs displayed extended blood circulation,improved tumor accumulation,and more significant anti-tumor efficacy compared with PSD NPs.Furthermore,PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil,indicating better safety.Therefore,this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.展开更多
Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seem...Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents,thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy.In this study,a series of weak acid drug derivatives were designed by a simplistic one step synthesis,which could be remotely loaded into liposomes by p H gradient method.Cabazitaxel(CTX)weak acid derivatives were selected to evaluate regarding its safety profiles,pharmacodynamics,and pharmacokinetics.CTX weak acid derivative liposomes were superior to Jevtanaa in terms of safety profiles,including systemic toxicity,hematological toxicity,and potential central nerve toxicity.Specifically,it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons.Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.展开更多
Targeted protein degradation(TPD)holds great promise for biological inquiry and therapeutic development.However,it still remains elusive to destruct DNA/RNA binding proteins(DBPs/RBPs)previously deemed undruggable.Her...Targeted protein degradation(TPD)holds great promise for biological inquiry and therapeutic development.However,it still remains elusive to destruct DNA/RNA binding proteins(DBPs/RBPs)previously deemed undruggable.Herein,we report ligandassisted covalent hydrophobic tagging(LACHT)as a modular strategy for TPD of these difficult-totarget proteins.Guided by a noncovalent protein ligand,LACHT leverages a reactive N-acyl-N-alkyl sulfonamide group to covalently label the protein target with a hydrophobic adamantane,which further engages the cellular quality control mechanism to induce proteolytic degradation.Using a smallmolecule ligand,we demonstrated that LACHT allowed TPD of a DBP,bromodomain-containing protein 4,in human leukemia cells with high efficiency.Mechanistic studies revealed that LACHT-mediated TPD dependent on ligand-directed irreversible tagging and the covalently labeled proteins underwent polyubiquitination before removal through both the proteasome and the lysosome.Furthermore,when an RNA ligand was employed,we showed that LACHT also enabled TPD of an RBP,Lin28a,leading to upregulation of its downstream let-7 miRNA.This study thus provides a generalizable platform to expand the TPD toolbox for biomedical applications.展开更多
In this paper,we propose a political-economy model of China that explains both the rapid economic growth and frequent rate of accidents that have occurred in China.The central government delegates authority to the loc...In this paper,we propose a political-economy model of China that explains both the rapid economic growth and frequent rate of accidents that have occurred in China.The central government delegates authority to the local government to regulate the production activities of the firm.Under information asymmetry,the local government can collude with the firm and choose"bad"technology,the use of which will lead to faster economic growth and more accidents than the use of"good"technology.We characterize optimal equilibrium within collusion contracts,under which the central government will allow collusion when the cost to eliminate collusion is high.We also characterize the optimal collusion-proof contract,under which the payments,reprimands,and taxes that take place between the local government and the firm are endogenously determined.Our predictions on collusion and growth are supported by an empirical study on the coal industry.展开更多
The windward bend lattice frame structure(WB structure)is characterized by a high heat transfer coefficient and low friction factor.The WB structure can be applied for ther-mal protection system,protecting outer walls...The windward bend lattice frame structure(WB structure)is characterized by a high heat transfer coefficient and low friction factor.The WB structure can be applied for ther-mal protection system,protecting outer walls of afterburner and nozzles from being damaged by the heating load of hot gas,for air cooling system of the power battery module,dissipating the heat generated during its charging and discharging.In this paper,the heat transfer charac-teristics of the windward bend lattice frame structure have been comprehensively studied.A systematic 3D numerical simulation has been conducted to investigate the effects of the struc-tural parameters of the WB structure,including the pitches in both flow direction and transverse direction,the diameter and the inclination angle of windward bend ligament,on its flow resis-tance and heat transfer enhancement,which has been evaluated by comparing its Nusselt num-ber under an equal pumping power.Furthermore,the contribution of an important parameter,i.e.,the ratio of the interstitial heat transfer rate to the end-wall heat transfer rate(RQ),to the overall heat transfer rate has been fully discussed.As a result,the case of 6 units in the longi-tudinal direction and 2.5 units in the transverse direction,i.e.(nx Z 6,nz Z 2.5)exhibits the best performance in the light of the value of the Nusselt number. Moreover, the structure with aratio of RQ ranges in 4.5e5.0 achieves a better heat transfer performance. Finally, two colorcontour graphs showing an optimal range of Nusselt number coordinated by unit numbers(nx, nz) for pumping powers of 2500 and 3000 have been presented. The graphs correctly reflectthe variation of Nusselt numbers of structures with different nx and nz, and the conclusionsremain consistent with the discussion in sections 4.2 and 4.3, instructing the reasonable selec-tion of structural parameters of a thermal protection system embedded with WB structure.展开更多
基金financially supported by the National Natural Science Foundation(31500323 41501583 31370426)
文摘This study investigates the effects of cold-acclimation in conferring chilling tolerance in seedlings of the mulberry(Morus alba) variety ‘Qiuyu’. Changes in photosynthesis and antioxidant enzymes in chilling acclimatized(CA), and non-acclimatized(NA) seedlings were recorded during chilling stress(3 °C) and a recovery period(25 °C) each for 3 days. The results showed that CA plants had higher net photosynthetic rates(P_n), stomatal conductance(G_s), and maximum photochemical efficiency of photosystem Ⅱ(F_v/F_m) in response to chilling stress compared to NA. The seedlings maintained the same trends during the recovery stage. The responses of Q_A reduction degree (1-q_P) and prime electronic transfer rates(F_o) were lower in acclimatized than in non-acclimatized seedlings. Low-temperature acclimation and chilling stress also caused an increase in leaf proline and soluble sugar contents. Leaf malondialdehyde levels were significantly lower while ascorbate peroxidase(APX) activity was significantly higher in acclimatized seedlings, suggesting that elevated osmolytes and APX confer resistance to chilling temperatures. In this study on the response of mulberry seedlings to chilling stress, we also looked at the recovery process. The response to chilling determines whether mulberry leaves can survive under cold temperatures, while the recovery process determines whether photosynthesis can recover as soon as possible to avoid any secondary damage.
基金supported by the National Natural Science Foundation of China(no.81872816)the Liaoning Revitalization Talents Program(no.XLYC180801)+1 种基金China Postdoctoral Innovative Talents Support Program(no.BX20190219)China Postdoctoral Science Foundation(no.2019M661134).
文摘Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid peroxidation.However,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis.Herein,a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin(DOX),iron and unsaturated lipid for efficient ferroptosis.By leveraging the coordination effect between DOX and Fe3+,trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method.First,Fe3+could react with the overexpressed GSH in tumor cells,inducing the GSH depletion and Fe2+generation.Second,the cleavage of trisulfide bond could also consume GSH,and the released DOX induces the generation of H2O2,which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis.Third,the formed Fe3+/Fe2+couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis.This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion,ROS generation and lipid peroxidation,providing new sights for efficient cancer therapy.
基金supported by the National Natural Science Foundation of China(Grant No.41974014)the Open Fund of State Laboratory of Information Engineering in Surveying,Mapping and Remote Sensing,Wuhan University(Grant No.19P01)+1 种基金the Foundation of Young Creative Talents in Higher Education of Guangdong Province(Grant No.2019KQNCX009)the Open Fund of Guangxi Key Laboratory of Spatial Information and Geomatics(Grant No.19-050-11-03)
文摘It is significant for identifying mass movement patterns to invert horizontal tectonic stresses at different depths underneath Tibet.In recent years,a large number of achievements focusing on two-dimensional tectonic stresses have been obtained from gravity data.However,three-dimensional tectonic stresses in Tibet are still unknown or debatable.Therefore,in the present study an improved method to multilayer horizontal tectonic stresses using gravity observations is developed.The inverted multilayer horizontal tectonic stresses are in agreement with those from previous studies.In addition,rich tectonic structure and development can be revealed from the inverted multilayer horizontal tectonic stresses:(1)the distribution of horizontal tectonic stresses at various depths shows strong correlation with that of the tectonic elements,where major faults and earthquake epicenters are corresponding with stress highs and the stable basins are consistent with stress lows.(2)the mass movement patterns of whole Tibet present clockwise,and the material movement directions in the west and east are approximately southnorth and east-west,respectively.(3)in eastern Tibet,the eastward materials caused by the south-north extrusion between Indian and Eurasian plates are divided into two parts by the stable Sichuan Block,one flowing nearly southeast and the other moving almost northeast.The inverted multilayer horizontal tectonic stresses may provide direct evidences for mass movement patterns in Tibet.
基金supported by the Fundamental Research Funds for the Central Universities(2572018BE05)the National Natural Science Foundation of China(3150032331370426)
文摘The solution culture method was used to study the effect of increasing nitrogen on the growth and pho-tosynthesis of poplar seedlings under 100 mmol L-1 NaCl stress. I Increase in nitrogen reduced stomatal limitation of leaves under NaCl stress, improved utilization of CO2 by mesophyll cells, enhanced photosynthetic carbon assimi-lation capacity, significantly alleviated saline damage of NaCl, and promoted the accumulation of aboveground and root biomass. I Increased nitrogen enhanced photochemical efficiency (ΦPSⅡ) and electron transport rates, relieved the reduction of maximum photochemical efficiency (Fv/Fm) under NaCl, and reduced the degree of photoinhibition caused by NaCl stress. Increased nitrogen applications reduced the proportion of energy dissipating in the form of ineffective heat energy and hence a greater proportion of light energy absorbed by leaves was allocated to photo-chemical reactions. Under treatment with increased nitro-gen, the synergistic effect of heat dissipation and the xanthophyll cycle in the leaves effectively protected pho-tosynthetic PSⅡ and enhanced light energy utilization of leaves under NaCl stress. The increased nitrogen promoted photosynthetic electron supply and transport ability under NaCl stress evident in enhanced functioning of the oxygen-evolving complex on the electron donor side of PS Ⅱ. It increased the ability of the receptor pool to accept electrons on the PSII electron acceptor side and improved the sta-bility of thylakoid membranes under NaCl stress. Therefore, increasing nitrogen applications under NaCl stress can promote poplar growth by improving the effi-ciency of light energy utilization.
文摘To construct pulsed high magnet, with rapid adjustments to large changes in the field strength, it is a mandatory acces-sory to development a special NMR probes to provide a precise real-time map of the magnetic field. In order to do so, it is necessary to understand the variations of the spin transition and susceptibility of NMR samples in a time dependent longitudinal field. This work analyzes the effect on the spin transition by a time dependent longitudinal field. For a 1/2 spin system, we have derived a simple formula for the prediction of the probabilities of occupation of the 1/2 and ?1/2 states in a non-static field. We also calculate the magnetic susceptibility of the water and give an analysis of the effect on the magnetic susceptibility in a time dependent longitudinal field and RF frequency.
文摘In recent years,through financial subsidies,Shouguang City has promoted the application of electrostatic sprayer,dual-purpose fog and mist sprinkler machine,Bacillus cereus,flame disinfection service based on fine rotary tillage and multi-functional plant protection machine and other new green prevention and control products and technologies for the greenhouse vegetable in the city. As a result,the utilization rate of pesticides was increased by more than 5%,and the application rate was reduced by more than 10%.
基金supported by an operating grant(No.BK2008440) to DSM from the Science and Technology Department of Jiangsu province,China
文摘The aim of the present study was to determine whether the sensitivity of thymocytes to X-ray radiation depends on their proliferative states and whether radiation impairs the maturation of donor-derived thymocytes in recipient thymus.We assigned 8-week-old C57BL/6J mice into three treatment groups:1) untreated;2) X-ray radiation;3) X-ray radiation plus bone marrow transplantation with donor bone marrow cells from transgenic mice express-ing enhanced green fluorescent protein(GFP) on a universal promoter.After 4 weeks,the size of the thymus,the number and proliferation of thymocytes and ratios of different stage thymocytes were analyzed by immunohisto-chemistry and flow cytometry.The results showed that:1) CD4+CD8+ thymocytes were more sensitive to X-ray radiation-induced cell death than other thymocytes;2) the proliferative capacity of CD4+CD8+ thymocytes was higher than that of other thymocytes;3) the size of the thymus,the number of thymocytes and ratios of thymo-cytes of different stages in irradiated mice recovered to the normal level of untreated mice by bone marrow trans-plantation;4) the ratio of GFP-positive CD4+CD8+ thymocytes increased significantly,whereas the ratio of GFP-positive CD4+ or CD8+ thymocytes decreased significantly.These results indicate that the degree of sensitivity of thymocytes to X-ray radiation depends on their proliferative states and radiation impairs the maturation of donor-derived CD4+CD8+ thymocytes in recipient thymus.
基金supported by the National Natural Science Foundation of China (Nos. 51874110 and 51604089)Natural Science Foundation of Heilongjiang Province (No. LH2021B011)Open Project of State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology (No. QA202138)。
文摘Lithium-sulfur(Li-S)batteries have been regarded as the candidate for the next-generation energy storage system due to the high theoretical specific capacity(1675 m Ah/g), energy density(2600 Wh/kg)and the abundance of elemental sulfur, but the application of Li-S batteries is impeded by a series of problems. Recently, all-solid-state Li-S batteries(ASSLSBs) have drawn great attention because many drawbacks such as safety issues caused by metallic lithium anodes and organic liquid electrolytes can be overcome through the use of solid-state electrolytes(SEs). However, not only the problems brought by sulfur cathodes still exist, but more trouble arouses from the interfaces between SEs and cathodes, hampering the practical application of ASSLSBs. Therefore, in order to deal with the problems, enormous endeavors have been done on ASSLSB cathodes during the past few decades, including engineering of cathode active materials, cathode host materials, cathode binder materials and cathode structures. In this review, the electrochemical mechanism and existing problems of ASSLSBs are briefly introduced. Subsequently, the strategies for developing cathode materials and designing cathode structures are presented. Then there follows a brief discussion of SE problems and expectations, and finally, the challenges and perspectives of ASSLSBs are summarized.
基金supported by the National Natural Science Foundation of China(81920108029,22077063,22322703)the Key Foundation for Social Development Project of Jiangsu Province of China(BE2021741)。
文摘Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.
基金supported by National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2017ZX09101-001-005,Beijing,China)Science and Technology Plan Project of Shenyang(No.18-400-4-08,Z17-5-064,China)the Career Development Program for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(Shenyang,China)
文摘The combination of paclitaxel(PTX)and doxorubicin(DOX)has been widely used in the clinic.However,it remains unsatisfied due to the generation of severe toxicity.Previously,we have successfully synthesized a prodrug PTX-S-DOX(PSD).The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX.Thus,we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation.Due to the fact that copper ions(Cu2+)could coordinate with the anthracene nucleus of DOX,we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+gradient.Hence,we designed a remote loading liposomal formulation of PSD(PSD LPs)for combination chemotherapy.The prepared PSD LPs displayed extended blood circulation,improved tumor accumulation,and more significant anti-tumor efficacy compared with PSD NPs.Furthermore,PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil,indicating better safety.Therefore,this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
基金financially supported by the National Nature Science Foundation of China(U1608283)the Career Development Program for Young and Middle-aged Teachers in Shenyang Pharmaceutical University
文摘Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents,thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy.In this study,a series of weak acid drug derivatives were designed by a simplistic one step synthesis,which could be remotely loaded into liposomes by p H gradient method.Cabazitaxel(CTX)weak acid derivatives were selected to evaluate regarding its safety profiles,pharmacodynamics,and pharmacokinetics.CTX weak acid derivative liposomes were superior to Jevtanaa in terms of safety profiles,including systemic toxicity,hematological toxicity,and potential central nerve toxicity.Specifically,it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons.Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.
基金supported by the Natural Science Foundation of Jiangsu Province(grant nos.BK20202004 and BE2022835)the National Natural Science Foundation of China(grant nos.22077063,22225703,22137003,21877058,and 21977043).
文摘Targeted protein degradation(TPD)holds great promise for biological inquiry and therapeutic development.However,it still remains elusive to destruct DNA/RNA binding proteins(DBPs/RBPs)previously deemed undruggable.Herein,we report ligandassisted covalent hydrophobic tagging(LACHT)as a modular strategy for TPD of these difficult-totarget proteins.Guided by a noncovalent protein ligand,LACHT leverages a reactive N-acyl-N-alkyl sulfonamide group to covalently label the protein target with a hydrophobic adamantane,which further engages the cellular quality control mechanism to induce proteolytic degradation.Using a smallmolecule ligand,we demonstrated that LACHT allowed TPD of a DBP,bromodomain-containing protein 4,in human leukemia cells with high efficiency.Mechanistic studies revealed that LACHT-mediated TPD dependent on ligand-directed irreversible tagging and the covalently labeled proteins underwent polyubiquitination before removal through both the proteasome and the lysosome.Furthermore,when an RNA ligand was employed,we showed that LACHT also enabled TPD of an RBP,Lin28a,leading to upregulation of its downstream let-7 miRNA.This study thus provides a generalizable platform to expand the TPD toolbox for biomedical applications.
基金the financial support from the Special Fund for Authors of National Excellent Doctoral DissertationChina Ministry of Education Fund for Young Scholars in Humanities and Social Science
文摘In this paper,we propose a political-economy model of China that explains both the rapid economic growth and frequent rate of accidents that have occurred in China.The central government delegates authority to the local government to regulate the production activities of the firm.Under information asymmetry,the local government can collude with the firm and choose"bad"technology,the use of which will lead to faster economic growth and more accidents than the use of"good"technology.We characterize optimal equilibrium within collusion contracts,under which the central government will allow collusion when the cost to eliminate collusion is high.We also characterize the optimal collusion-proof contract,under which the payments,reprimands,and taxes that take place between the local government and the firm are endogenously determined.Our predictions on collusion and growth are supported by an empirical study on the coal industry.
基金The authors are grateful for financial support from grant of National Science Foundation of China(No.52006179)from the Fundamental Research Funds for the Central Universities(31020190QD706 and 3102020OMS701)from the National Science and Technology Major Project(J2019-III-0019-0063).
文摘The windward bend lattice frame structure(WB structure)is characterized by a high heat transfer coefficient and low friction factor.The WB structure can be applied for ther-mal protection system,protecting outer walls of afterburner and nozzles from being damaged by the heating load of hot gas,for air cooling system of the power battery module,dissipating the heat generated during its charging and discharging.In this paper,the heat transfer charac-teristics of the windward bend lattice frame structure have been comprehensively studied.A systematic 3D numerical simulation has been conducted to investigate the effects of the struc-tural parameters of the WB structure,including the pitches in both flow direction and transverse direction,the diameter and the inclination angle of windward bend ligament,on its flow resis-tance and heat transfer enhancement,which has been evaluated by comparing its Nusselt num-ber under an equal pumping power.Furthermore,the contribution of an important parameter,i.e.,the ratio of the interstitial heat transfer rate to the end-wall heat transfer rate(RQ),to the overall heat transfer rate has been fully discussed.As a result,the case of 6 units in the longi-tudinal direction and 2.5 units in the transverse direction,i.e.(nx Z 6,nz Z 2.5)exhibits the best performance in the light of the value of the Nusselt number. Moreover, the structure with aratio of RQ ranges in 4.5e5.0 achieves a better heat transfer performance. Finally, two colorcontour graphs showing an optimal range of Nusselt number coordinated by unit numbers(nx, nz) for pumping powers of 2500 and 3000 have been presented. The graphs correctly reflectthe variation of Nusselt numbers of structures with different nx and nz, and the conclusionsremain consistent with the discussion in sections 4.2 and 4.3, instructing the reasonable selec-tion of structural parameters of a thermal protection system embedded with WB structure.