To assess the high-temperature creep properties of titanium matrix composites for aircraft skin,the TA15 alloy,TiB/TA15 and TiB/(TA15−Si)composites with network structure were fabricated using low-energy milling and v...To assess the high-temperature creep properties of titanium matrix composites for aircraft skin,the TA15 alloy,TiB/TA15 and TiB/(TA15−Si)composites with network structure were fabricated using low-energy milling and vacuum hot pressing sintering techniques.The results show that introducing TiB and Si can reduce the steady-state creep rate by an order of magnitude at 600℃ compared to the alloy.However,the beneficial effect of Si can be maintained at 700℃ while the positive effect of TiB gradually diminishes due to the pores near TiB and interface debonding.The creep deformation mechanism of the as-sintered TiB/(TA15−Si)composite is primarily governed by dislocation climbing.The high creep resistance at 600℃ can be mainly attributed to the absence of grain boundaryαphases,load transfer by TiB whisker,and the hindrance of dislocation movement by silicides.The low steady-state creep rate at 700℃ is mainly resulted from the elimination of grain boundaryαphases as well as increased dynamic precipitation of silicides andα_(2).展开更多
The sediments of crater lakes are one of the ideal archives for high-resolution paleoenvironmental reconstruction.This paper presents sedimentary records of 21 crater lakes in monsoonal China and systematically discus...The sediments of crater lakes are one of the ideal archives for high-resolution paleoenvironmental reconstruction.This paper presents sedimentary records of 21 crater lakes in monsoonal China and systematically discusses the geographical distribution and formation ages of these crater lakes.Sediment provenance of the crater lakes and its influencing factors were analyzed,and paleoenvironmental sequences and human activities records on different timescales reconstructed by crater lake sediments in monsoonal China were reviewed.The following points are highlighted:(1)Crater lakes in monsoonal China have been shown to preserve continuous long-time sediments that can exceed even 400 ka,although the chronology of some sediments in the southern part is debated and there were currently fewer long time records from the northern part;(2)the sediment provenance of crater lakes in northern China(e.g.,aeolian inputs)was different from that in the south(e.g.,the volcanic-lake rim),due to the different location and deposition conditions of crater lakes;(3)crater lake sediments have been used to reconstruct the history of climate changes on different timescales,but reconstruction studies of glacial-interglacial and decadal-annual scale records and studies of spatial comparisons of records on different timescales still need to be strengthened;(4)the anthropogenic signals,which include cultivation,logging,and industrial activity,are well documented in crater lake sediments from different areas and can therefore provide key evidence for the study of the Anthropocene.展开更多
The enhancement of coercivity in Nd-Fe-B sintered magnets modified by Pr_(58)Dy_(10)Cu_(32)alloy was investigated through scanning electron microscope(SEM)and in-situ magneto-optic Kerr effect(MOKE)microscopy.The modi...The enhancement of coercivity in Nd-Fe-B sintered magnets modified by Pr_(58)Dy_(10)Cu_(32)alloy was investigated through scanning electron microscope(SEM)and in-situ magneto-optic Kerr effect(MOKE)microscopy.The modification treatment resulted in the formation of a smooth and continuous weakly magnetic grain boundary layer and the(Nd,Pr,Dy)_(2)Fe_(14)B main phase with a high magnetocrystalline anisotropy field,leading to an increased coercivity of 23 kOe.MOKE observations revealed that the dynamic evolution of the maze domain area under an external magnetic field varied significantly between the original and modified magnets.Compared with the original magnets,the modified magnets exhibited a slower decrease in maze domain area during magnetization and a slower increase during reverse magnetization,contributing to the observed coercivity enhancement.展开更多
Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous syste...Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].展开更多
BACKGROUND Colorectal laterally spreading tumors(LSTs)with malignant potential require en bloc resection by endoscopic submucosal dissection(ESD),but lesions with deep submucosal invasion(SMI)are endoscopically unrese...BACKGROUND Colorectal laterally spreading tumors(LSTs)with malignant potential require en bloc resection by endoscopic submucosal dissection(ESD),but lesions with deep submucosal invasion(SMI)are endoscopically unresectable.AIM To investigate the factors associated with high-grade dysplasia(HGD)/carcinoma and deep SMI in colorectal LSTs.METHODS The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed.The characteristics of LST subtypes were compared.Risk factors for HGD/carcinoma and deep SMI(invasion depth≥1000μm)were determined using multivariate logistic regression.RESULTS A total of 323 patients with 341 colorectal LSTs were enrolled.Among the four subtypes,non-granular pseudodepressed(NG-PD)LSTs(85.5%)had the highest rate of HGD/carcinoma,followed by the granular nodular mixed(G-NM)(77.0%),granular homogenous(29.5%),and non-granular flat elevated(24.2%)subtypes.Deep SMI occurred commonly in NG-PD LSTs(12.9%).In the adjusted multivariate analysis,NG-PD[odds ratio(OR=16.8,P<0.001)and G-NM(OR=7.8,P<0.001)subtypes],size≥2 cm(OR=2.2,P=0.005),and positive non-lifting sign(OR=3.3,P=0.024)were independently associated with HGD/carcinoma.The NG-PD subtype(OR=13.3,P<0.001)and rectosigmoid location(OR=8.7,P=0.007)were independent risk factors for deep SMI.CONCLUSION Because of their increased risk for malignancy,it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD.Given their substantial risk for deep SMI,surgery needs to be considered for NG-PD LSTs located in the rectosigmoid,especially those with positive nonlifting signs.展开更多
Constructing a model for international carbon emissions trading is an effective method to curb global warming through a market mechanism.Although the international carbon emissions market generates substantial profits...Constructing a model for international carbon emissions trading is an effective method to curb global warming through a market mechanism.Although the international carbon emissions market generates substantial profits,the relevant trading mechanism has been far from perfect.The perfect mechanism for international carbon emissions trading should be a revealing preference game.In other words,only if all players in this game truly show their information and preferences can the Nash outcome be Pareto efficient and fair.China should actively participate in the international carbon emissions trading game;promote efficiency,justice,rationality,and the quality of being manipulation-free in the carbon emissions market;and play a more important role in perfecting the international carbon emissions trading mechanism.展开更多
Several studies have suggested the pivotal roles of eutrophic lakes in carbon(C)cycling at regional and global scales.However,how the co-metabolism effect on lake sediment organic carbon(OC)mineralization changes in r...Several studies have suggested the pivotal roles of eutrophic lakes in carbon(C)cycling at regional and global scales.However,how the co-metabolism effect on lake sediment organic carbon(OC)mineralization changes in response to integrated inputs of labile OC and nutrients is poorly understood.This knowledge gap hinders our ability to predict the carbon sequestration potential in eutrophic lakes.Therefore,a 45-day microcosm experiment was conducted to examine the dominant mechanisms that underpin the co-metabolism response to the inputs of labile C and nutrients in lacustrine sediments.Results indicate that the labile C addition caused a rapid increase in the positive co-metabolism effect during the initial stage of incubation,and the co-metabolism effect was positively correlated with the C input level.The positive co-metabolism effect was consistently higher under high C input,which was 152%higher than that under low C input.The higherβ-glucosidase activity after nutrient addition,which,in turn,promoted the OC mineralization in sediments.In addition different impacts of nutrients on the co-metabolism effect under different C inputs were observed.Compared with the low nutrient treatments,the largest co-metabolism effect under high C with high nutrient treatment was observed by the end of the incubation.In the high C treatment,the intensity of the co-metabolism effect(CE)under high nitrogen treatment was 1.88 times higher than that under low nitrogen condition.However,in the low C treatment,the amount of nitrogen had limited impact on co-metabolism effect.Our study thus proved that the microorganisms obviously regulate sediment OC turnover via stoichiometric flexibility to maintain a balance between resources and microbial requirements,which is meaningful for evaluating the OC budget and lake eutrophication management in lacustrine sediments.展开更多
The encapsulation of lunar samples is a core research area in the third phase of the Chinese Lunar Exploration Program.The seal assembly,opening and closing mechanism(OCM),and locking mechanism are the core components...The encapsulation of lunar samples is a core research area in the third phase of the Chinese Lunar Exploration Program.The seal assembly,opening and closing mechanism(OCM),and locking mechanism are the core components of the encapsulation device of the lunar samples,and the requirements of a tight seal,lightweight,and low power make the design of these core components difficult.In this study,a combined sealing assembly,OCM,and locking mechanism were investigated for the device.The sealing architecture consists of rubber and an Ag-In alloy,and a theory was built to analyze the seal.Experiments of the electroplate Au coating on the knife-edge revealed that the hermetic seal can be significantly improved.The driving principle for coaxial double-helical pairs was investigated and used to design the OCM.Moreover,a locking mechanism was created using an electric initiating explosive device with orifice damping.By optimizing the design,the output parameters were adjusted to meet the requirements of the lunar explorer.The experimental results showed that the helium leak rate of the test pieces were not more than 5×10^(-11) Pa·m^(3)·s^(-1),the minimum power of the OCM was 0.3 W,and the total weight of the principle prototype was 2.9 kg.The explosive driven locking mechanism has low impact.This investigation solved the difficulties in achieving tight seal,light weight,and low power for the lunar explorer,and the results can also be used to explore other extraterrestrial objects in the future.展开更多
The acceleration of decay induced by frequency measurements,namely the quantum anti-Zeno effect(AZE),was first predicted by Kofman and Kurizki [Nature 405(2000) 546].The effect of the frequency measurements on nuclear...The acceleration of decay induced by frequency measurements,namely the quantum anti-Zeno effect(AZE),was first predicted by Kofman and Kurizki [Nature 405(2000) 546].The effect of the frequency measurements on nuclear β decay rate is analyzed based on the time-dependent perturbation theory.We present a detailed calculation of the decay rates of ^(3)H,^(60)Co(β^(-)type),^(22)Na,^(106)Ag(β^(+) type) and ^(18)F,^(57)Co and ^(111)Sn(EC type)under frequency measurements.It is found that the effects of frequency measurements on the decay rates of β^(+)and β^(-)cases are different from the case of EC,and the smaller the β decay energy is,the more favorable it is to observe the AZE in experiment.Based on our analysis,it is suggested that possible experimental candidates should have a small decay energy and a reasonable half life(such as ^(3)H) for observing the AZE in β decay.展开更多
Glioma is difficult to treat due to the unique tumor microenvironment and bloodebrain barrier.(13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]indolizidine(PF403),a phenanthroindolizidine alkaloid,has been identified ...Glioma is difficult to treat due to the unique tumor microenvironment and bloodebrain barrier.(13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]indolizidine(PF403),a phenanthroindolizidine alkaloid,has been identified as a promising therapeutic agent for the treatment of glioma.However,the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated.Hence,a strategy without chemical modification was applied to identify the target of PF403.In this study,we identified nicotinamide phosphoribosyl transferase(NAMPT)as the target of PF403 by using thermal proteome profiling(TPP).Moreover,microscale thermophoresis(MST),surface plasmon resonance(SPR),and isothermal titration calorimetry(ITC)experiments confirmed that NAMPT exhibits good affinity for PF403.Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT,leading to a decrease in the concentration of nicotinamide adenine dinucleotide(NAD ^(+))in U87 cells.X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of piepi interactions with residue Tyr188 to maintain binding with NAMPT(PDB code 8Y55).After NAMPT was knocked down with lentivirus,PF403 lost or partially lost its antitumor activity at the cellular and animal levels.These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.展开更多
When sudden disasters such as earthquakes and tsunamis culminate in the outage of control systems in nuclear power plants,the operators may be exposed to extremely hot-humid environmental conditions while still facing...When sudden disasters such as earthquakes and tsunamis culminate in the outage of control systems in nuclear power plants,the operators may be exposed to extremely hot-humid environmental conditions while still facing demanding cognitive tasks.To investigate how their cognitive performance is related to their heart rate variability(HRV),we exposed nuclear power plant operators to four high temperature and humidity environments and measured their HRV during seven different cognitive tasks for 30 min.Generalized linear mixed-effects models(GLMMs)are used to analyze the relationship between HRV and operators'cognitive performance.Studies have shown that all indicators of HRV have a significant impact on the cognitive ability of operators.In both the low frequency(LF)and high frequency(HF),especially in the very low frequency(VLF)domain,HRV significantly correlates with the operator's cognition.Although the cognitive performance aggravates slightly within 30 min,increasing the humidity under fixed high temperatures does not exhibit an overall effect on cognitive performance.Henceforth,this study provides a guidance for safety limits of the operator's working duration.Moreover,VLF,LF,and HF domains might be potential physiological indicators to monitor the cognitive ability of operators.展开更多
Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of thi...Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently.Here,we showed that IMMH002,a novel orally active S1 P1 modulator,desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus.Using different psoriasis animal models,we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PAS I score and pathological injure evaluation.Mechanistically,IMMH002 regulated CD3+T lymphocytes re-distribution by inducing lymphocytes’homing,thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus.Our results suggest that the novel SIP1 agonist,IMMH002,exert extraordinary capacity to rapidly modulate T lymphocytes distribution,representing a promising drug candidate for psoriasis treatment.展开更多
Tumor-associated macrophages(TAMs)generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis,suggesting their potential value as a target in cancer immunotherapy.Chlorogenic acid(...Tumor-associated macrophages(TAMs)generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis,suggesting their potential value as a target in cancer immunotherapy.Chlorogenic acid(CHA)has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype.However,rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials.In this study,mannosylated liposomes are developed for targeted delivery of CHA to TAMs.The immunoregulatory effects of CHA,along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes,are investigated through in vitro and in vivo experiments.The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size,favorable stability,and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects.Further,CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype.Overall,these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.展开更多
基金financially supported by the National Key R&D Program of China(No.2022YFB3707405)the National Natural Science Foundation of China(Nos.U22A20113,52171137,52071116)+1 种基金Heilongjiang Provincial Natural Science Foundation,China(No.TD2020E001)Heilongjiang Touyan Team Program,China.
文摘To assess the high-temperature creep properties of titanium matrix composites for aircraft skin,the TA15 alloy,TiB/TA15 and TiB/(TA15−Si)composites with network structure were fabricated using low-energy milling and vacuum hot pressing sintering techniques.The results show that introducing TiB and Si can reduce the steady-state creep rate by an order of magnitude at 600℃ compared to the alloy.However,the beneficial effect of Si can be maintained at 700℃ while the positive effect of TiB gradually diminishes due to the pores near TiB and interface debonding.The creep deformation mechanism of the as-sintered TiB/(TA15−Si)composite is primarily governed by dislocation climbing.The high creep resistance at 600℃ can be mainly attributed to the absence of grain boundaryαphases,load transfer by TiB whisker,and the hindrance of dislocation movement by silicides.The low steady-state creep rate at 700℃ is mainly resulted from the elimination of grain boundaryαphases as well as increased dynamic precipitation of silicides andα_(2).
基金supported by the National Natural Science Foundation of China(Nos.41888101,41721002)the National Key Research and Development Program of China(No.2022YFF0801101)+2 种基金the Fundamental Research Funds for the Central Universities,the China Postdoctoral Science Foundation(No.2022M713024)the CAS Youth Interdisciplinary Team(No.JCTD-2021-05)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2018498).
文摘The sediments of crater lakes are one of the ideal archives for high-resolution paleoenvironmental reconstruction.This paper presents sedimentary records of 21 crater lakes in monsoonal China and systematically discusses the geographical distribution and formation ages of these crater lakes.Sediment provenance of the crater lakes and its influencing factors were analyzed,and paleoenvironmental sequences and human activities records on different timescales reconstructed by crater lake sediments in monsoonal China were reviewed.The following points are highlighted:(1)Crater lakes in monsoonal China have been shown to preserve continuous long-time sediments that can exceed even 400 ka,although the chronology of some sediments in the southern part is debated and there were currently fewer long time records from the northern part;(2)the sediment provenance of crater lakes in northern China(e.g.,aeolian inputs)was different from that in the south(e.g.,the volcanic-lake rim),due to the different location and deposition conditions of crater lakes;(3)crater lake sediments have been used to reconstruct the history of climate changes on different timescales,but reconstruction studies of glacial-interglacial and decadal-annual scale records and studies of spatial comparisons of records on different timescales still need to be strengthened;(4)the anthropogenic signals,which include cultivation,logging,and industrial activity,are well documented in crater lake sediments from different areas and can therefore provide key evidence for the study of the Anthropocene.
基金supported by the National Key Research and Development Program of China(Grant Nos.2021YFB3500300,2023YFB3507000,and 2023XYJG0001-01-03)the National Natural Science Foundation of China(Grant No.52171167)Inner Mongolia Northern Rare Earth Advanced Materials Technology Innovation Co.,Ltd.Project(Grant No.CXZX-B-202304-0004).
文摘The enhancement of coercivity in Nd-Fe-B sintered magnets modified by Pr_(58)Dy_(10)Cu_(32)alloy was investigated through scanning electron microscope(SEM)and in-situ magneto-optic Kerr effect(MOKE)microscopy.The modification treatment resulted in the formation of a smooth and continuous weakly magnetic grain boundary layer and the(Nd,Pr,Dy)_(2)Fe_(14)B main phase with a high magnetocrystalline anisotropy field,leading to an increased coercivity of 23 kOe.MOKE observations revealed that the dynamic evolution of the maze domain area under an external magnetic field varied significantly between the original and modified magnets.Compared with the original magnets,the modified magnets exhibited a slower decrease in maze domain area during magnetization and a slower increase during reverse magnetization,contributing to the observed coercivity enhancement.
基金the National Natural Science Foundation of China(81871852,81200935,81671867 and 81971794)the Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Returned Scholars of the Ministry of Education of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
文摘Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].
基金Supported by Beijing Nova Program,No.Z201100006820147Beijing Municipal Administration of Hospitals’Youth Program,No.QML20180102。
文摘BACKGROUND Colorectal laterally spreading tumors(LSTs)with malignant potential require en bloc resection by endoscopic submucosal dissection(ESD),but lesions with deep submucosal invasion(SMI)are endoscopically unresectable.AIM To investigate the factors associated with high-grade dysplasia(HGD)/carcinoma and deep SMI in colorectal LSTs.METHODS The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed.The characteristics of LST subtypes were compared.Risk factors for HGD/carcinoma and deep SMI(invasion depth≥1000μm)were determined using multivariate logistic regression.RESULTS A total of 323 patients with 341 colorectal LSTs were enrolled.Among the four subtypes,non-granular pseudodepressed(NG-PD)LSTs(85.5%)had the highest rate of HGD/carcinoma,followed by the granular nodular mixed(G-NM)(77.0%),granular homogenous(29.5%),and non-granular flat elevated(24.2%)subtypes.Deep SMI occurred commonly in NG-PD LSTs(12.9%).In the adjusted multivariate analysis,NG-PD[odds ratio(OR=16.8,P<0.001)and G-NM(OR=7.8,P<0.001)subtypes],size≥2 cm(OR=2.2,P=0.005),and positive non-lifting sign(OR=3.3,P=0.024)were independently associated with HGD/carcinoma.The NG-PD subtype(OR=13.3,P<0.001)and rectosigmoid location(OR=8.7,P=0.007)were independent risk factors for deep SMI.CONCLUSION Because of their increased risk for malignancy,it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD.Given their substantial risk for deep SMI,surgery needs to be considered for NG-PD LSTs located in the rectosigmoid,especially those with positive nonlifting signs.
基金This work was funded by Humanity and Social Science Youth foundation of Ministry of Education of China:Research on the Practices and Theoretical Innovation of Improving People's Wellbeing in the New Era[Grant number.18YJC710023]Major Projects of Social Science Fund of Jilin University:Research on China's Social Welfare System[Grant number.2019XXJD10]Major Projects of Trade Union of Jilin Province:Research on the Evaluation System of Harmonious Labor Relations[Grant number.2016LD007].
文摘Constructing a model for international carbon emissions trading is an effective method to curb global warming through a market mechanism.Although the international carbon emissions market generates substantial profits,the relevant trading mechanism has been far from perfect.The perfect mechanism for international carbon emissions trading should be a revealing preference game.In other words,only if all players in this game truly show their information and preferences can the Nash outcome be Pareto efficient and fair.China should actively participate in the international carbon emissions trading game;promote efficiency,justice,rationality,and the quality of being manipulation-free in the carbon emissions market;and play a more important role in perfecting the international carbon emissions trading mechanism.
基金Supported by the National Natural Science Foundation of China(No.42077294)the Special basic research service for the Central Level Public Welfare Research Institute(No.GYZX210517)+1 种基金the Major Science and Technology Program for Water Pollution Control and Treatment(Nos.2017ZX07203-003,2017ZX07301006)the Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province(No.gxyqZD2020047)。
文摘Several studies have suggested the pivotal roles of eutrophic lakes in carbon(C)cycling at regional and global scales.However,how the co-metabolism effect on lake sediment organic carbon(OC)mineralization changes in response to integrated inputs of labile OC and nutrients is poorly understood.This knowledge gap hinders our ability to predict the carbon sequestration potential in eutrophic lakes.Therefore,a 45-day microcosm experiment was conducted to examine the dominant mechanisms that underpin the co-metabolism response to the inputs of labile C and nutrients in lacustrine sediments.Results indicate that the labile C addition caused a rapid increase in the positive co-metabolism effect during the initial stage of incubation,and the co-metabolism effect was positively correlated with the C input level.The positive co-metabolism effect was consistently higher under high C input,which was 152%higher than that under low C input.The higherβ-glucosidase activity after nutrient addition,which,in turn,promoted the OC mineralization in sediments.In addition different impacts of nutrients on the co-metabolism effect under different C inputs were observed.Compared with the low nutrient treatments,the largest co-metabolism effect under high C with high nutrient treatment was observed by the end of the incubation.In the high C treatment,the intensity of the co-metabolism effect(CE)under high nitrogen treatment was 1.88 times higher than that under low nitrogen condition.However,in the low C treatment,the amount of nitrogen had limited impact on co-metabolism effect.Our study thus proved that the microorganisms obviously regulate sediment OC turnover via stoichiometric flexibility to maintain a balance between resources and microbial requirements,which is meaningful for evaluating the OC budget and lake eutrophication management in lacustrine sediments.
基金Supported by Research Foundation of CLEP of China (Grant No.TY3Q20110003)。
文摘The encapsulation of lunar samples is a core research area in the third phase of the Chinese Lunar Exploration Program.The seal assembly,opening and closing mechanism(OCM),and locking mechanism are the core components of the encapsulation device of the lunar samples,and the requirements of a tight seal,lightweight,and low power make the design of these core components difficult.In this study,a combined sealing assembly,OCM,and locking mechanism were investigated for the device.The sealing architecture consists of rubber and an Ag-In alloy,and a theory was built to analyze the seal.Experiments of the electroplate Au coating on the knife-edge revealed that the hermetic seal can be significantly improved.The driving principle for coaxial double-helical pairs was investigated and used to design the OCM.Moreover,a locking mechanism was created using an electric initiating explosive device with orifice damping.By optimizing the design,the output parameters were adjusted to meet the requirements of the lunar explorer.The experimental results showed that the helium leak rate of the test pieces were not more than 5×10^(-11) Pa·m^(3)·s^(-1),the minimum power of the OCM was 0.3 W,and the total weight of the principle prototype was 2.9 kg.The explosive driven locking mechanism has low impact.This investigation solved the difficulties in achieving tight seal,light weight,and low power for the lunar explorer,and the results can also be used to explore other extraterrestrial objects in the future.
基金Supported by the National Natural Science Foundation of China(Grant Nos.11822503 and 11575082)the Fundamental Research Funds for the Central Universities(Nanjing University)。
文摘The acceleration of decay induced by frequency measurements,namely the quantum anti-Zeno effect(AZE),was first predicted by Kofman and Kurizki [Nature 405(2000) 546].The effect of the frequency measurements on nuclear β decay rate is analyzed based on the time-dependent perturbation theory.We present a detailed calculation of the decay rates of ^(3)H,^(60)Co(β^(-)type),^(22)Na,^(106)Ag(β^(+) type) and ^(18)F,^(57)Co and ^(111)Sn(EC type)under frequency measurements.It is found that the effects of frequency measurements on the decay rates of β^(+)and β^(-)cases are different from the case of EC,and the smaller the β decay energy is,the more favorable it is to observe the AZE in experiment.Based on our analysis,it is suggested that possible experimental candidates should have a small decay energy and a reasonable half life(such as ^(3)H) for observing the AZE in β decay.
基金supported financially by the National Natural Science Foundation of China(No.22337007).
文摘Glioma is difficult to treat due to the unique tumor microenvironment and bloodebrain barrier.(13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]indolizidine(PF403),a phenanthroindolizidine alkaloid,has been identified as a promising therapeutic agent for the treatment of glioma.However,the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated.Hence,a strategy without chemical modification was applied to identify the target of PF403.In this study,we identified nicotinamide phosphoribosyl transferase(NAMPT)as the target of PF403 by using thermal proteome profiling(TPP).Moreover,microscale thermophoresis(MST),surface plasmon resonance(SPR),and isothermal titration calorimetry(ITC)experiments confirmed that NAMPT exhibits good affinity for PF403.Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT,leading to a decrease in the concentration of nicotinamide adenine dinucleotide(NAD ^(+))in U87 cells.X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of piepi interactions with residue Tyr188 to maintain binding with NAMPT(PDB code 8Y55).After NAMPT was knocked down with lentivirus,PF403 lost or partially lost its antitumor activity at the cellular and animal levels.These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.
基金supported by the National Natural Science Foundation of China(No.72374118,72304165,72204136)the Beijing Natural Science Foundation(No.L243005)the assistance provided by the State Key Laboratory of Nuclear Power Safety Technology and Equipment,China Nuclear Power Engineering Co.,Ltd.(No.K-A2021.402).
文摘When sudden disasters such as earthquakes and tsunamis culminate in the outage of control systems in nuclear power plants,the operators may be exposed to extremely hot-humid environmental conditions while still facing demanding cognitive tasks.To investigate how their cognitive performance is related to their heart rate variability(HRV),we exposed nuclear power plant operators to four high temperature and humidity environments and measured their HRV during seven different cognitive tasks for 30 min.Generalized linear mixed-effects models(GLMMs)are used to analyze the relationship between HRV and operators'cognitive performance.Studies have shown that all indicators of HRV have a significant impact on the cognitive ability of operators.In both the low frequency(LF)and high frequency(HF),especially in the very low frequency(VLF)domain,HRV significantly correlates with the operator's cognition.Although the cognitive performance aggravates slightly within 30 min,increasing the humidity under fixed high temperatures does not exhibit an overall effect on cognitive performance.Henceforth,this study provides a guidance for safety limits of the operator's working duration.Moreover,VLF,LF,and HF domains might be potential physiological indicators to monitor the cognitive ability of operators.
基金supported by the CAMS Innovation Fund for Medical Sciences(2016-I2M-3-008,China)National Natural Science Foundation of China(NSFC Nos.81872923 and 81473096)+1 种基金Beijing Natural Science Foundation(No.7172140,China)The Drug Innovation Major Project(No.2018ZX09711001-003,China).
文摘Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently.Here,we showed that IMMH002,a novel orally active S1 P1 modulator,desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus.Using different psoriasis animal models,we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PAS I score and pathological injure evaluation.Mechanistically,IMMH002 regulated CD3+T lymphocytes re-distribution by inducing lymphocytes’homing,thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus.Our results suggest that the novel SIP1 agonist,IMMH002,exert extraordinary capacity to rapidly modulate T lymphocytes distribution,representing a promising drug candidate for psoriasis treatment.
基金financially supported by the National Science and Technology Major Project of China(Grant No.2018ZX09721003 , 2018ZX09711001)the Fundamental Research Funds for the Central Universities(Grant No.3332019069)the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.81703566).
文摘Tumor-associated macrophages(TAMs)generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis,suggesting their potential value as a target in cancer immunotherapy.Chlorogenic acid(CHA)has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype.However,rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials.In this study,mannosylated liposomes are developed for targeted delivery of CHA to TAMs.The immunoregulatory effects of CHA,along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes,are investigated through in vitro and in vivo experiments.The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size,favorable stability,and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects.Further,CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype.Overall,these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.
