The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapi...The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.展开更多
Hypoxia-induced factor-1 alpha (HIF-1α) affects many effector molecules and regulates tumor lymphangio- genesis and angiogenesis during hypoxia. The aim of this study was to investigate the role of HIF-1α in the r...Hypoxia-induced factor-1 alpha (HIF-1α) affects many effector molecules and regulates tumor lymphangio- genesis and angiogenesis during hypoxia. The aim of this study was to investigate the role of HIF-1α in the regu- lation of vascular endothelial growth factor C (VEGF-C) expression and its effect on lymphangiogenesis and an- giogenesis in breast cancer. Lymphatic vessel density (LVD), microvessel density (MVD) and the expressions of HIF-1α and VEGF-C proteins were evaluated by immunohistochemistry in 75 breast cancer samples. There was a significant correlation between HIF-1α and VEGF-C (P = 0.014, r = 0.273, Spearman's coefficient of correlation). HIF-1α and VEGF-C overexpression was significantly correlated with higher LVD (P = 0.003 and P = 0.017, re- spectively), regional lymph nodal involvement (P = 0.002 and P = 0.004, respectively) and advanced tumor, node, metastasis (TNM) classification (P = 0.001 and P = 0.01, respectively). Higher MVD was observed in the group expressing higher levels of HIF-1α and VEGF-C (P = 0.033 and P = 0.037, respectively). Univariate analysis showed shorter survival time in patients expressing higher levels of HIF-1α and VEGF-C. HIF-1α was also found to be an independent prognostic factor of overall survival in multivariate analysis. The results suggest that HIF-1α may affect VEGF-C expression, thus acting as a crucial regulator of lymphangiogenesis and angiogenesis in breast cancer. This study highlights promising potential of HIF- 1α as a therapeutic target against tumor lymph node me- tastasis.展开更多
We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.Th...We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.The CD44+CD24-/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant(TAM-R) cells.Cell cycle,apoptosis,STAT3 and phospho-STAT3 changes were observed af-ter treatment with tamoxifen.Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed.CD44+CD24-/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7.The CD44+CD24-/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7.Cell cycle changes,anti-apoptotic effects and STAT3 changes were also found.Mean-while,the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen.It is concluded that STAT3 plays an essential role in breast cancer stem cells,which correlated with tamoxifen resistance.展开更多
Simultaneous photothermal therapy(PTT)and photodynamic therapy(PDT)is beneficial for enhanced cancer therapy due to the synergistic effect.Conventional materials developed for synergistic PTT/PDT are generally multico...Simultaneous photothermal therapy(PTT)and photodynamic therapy(PDT)is beneficial for enhanced cancer therapy due to the synergistic effect.Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources.The emerging monocomponent diketopyrrolopyrrole(DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation,but suffer from low singlet oxygen quantum yield,which severely restricts the therapeutic efficacy.Herein,we report acceptor-oriented molecular design of a donor-acceptor-donor(D-A-D)conjugated small molecule(IID-ThTPA)-based phototheranostic agent,with isoindigo(IID)as selective acceptor and triphenylamine(TPA)as donor.The strong D-A strength and narrow singlet-triplet energy gap endow IID-ThTPA nanoparticles(IID-ThTPA NPs)high mass extinction coefficient(18.2 L g^-1 cm^-1),competitive photothermal conversion efficiency(35.4%),and a dramatically enhanced singlet oxygen quantum yield(84.0%)comparing with previously reported monocomponent PTT/PDT agents.Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.展开更多
Dropshafts are vertical structures widely used in urban drainage systems and buildings for water transportation.In this paper,a physical model study was conducted to investigate the air entrainment in the dropshaft un...Dropshafts are vertical structures widely used in urban drainage systems and buildings for water transportation.In this paper,a physical model study was conducted to investigate the air entrainment in the dropshaft under various flow regimes with and without air ventilation.Observed from the experiments,the air entrainment mechanisms varied with the water flow regimes in the dropshaft.When there was no water plug formed in the dropshaft,air could be supplied directly from downstream.Once the water plug was formed,while without venting,the air was replenished only from downstream intermittently and then in the form of large air bubble traveling upwards to the airspace at the top;while with venting,air was mainly replenished from the dropshaft top and no large air bubble was observed.The experimental results also showed that the amount of entrained air in the dropshaft with venting was greater than that without venting.展开更多
OBJECTIVE We want to investigate the mechanism of organophosphate-induced delayed neuropathy(OPIDN) and find appropriate therapeutic medicine.OPIDN,often leads to paresthesias,ataxia and paralysis,occurs in the late-s...OBJECTIVE We want to investigate the mechanism of organophosphate-induced delayed neuropathy(OPIDN) and find appropriate therapeutic medicine.OPIDN,often leads to paresthesias,ataxia and paralysis,occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate(OP) insecticides or nerve agents,and may contribute to the Gulf War Syndrome.METHODS FDSS Ca2^(+)-influx assays,single-cell calcium imaging and patch-clamp electrophysiology were the major testing techniques.Transfected HEK293 cells and dorsal root ganglion(DRG) neurons were used to evaluate the effects of compounds.Wild type and trpa1 knockout mice and adult hyline brown hens were used to evaluate the neuropathological damages caused by the OPs.Transmission electron microscopy imaging was used to observe the nerve injuries ultrastructurally.High-throughput screen for TRPA1 inhibitors was accomplished by Ion Works Barracuda(IWB) automated electrophysiology assay.RESULTS TRPA1(Transient receptor potential cation channel,member A1) channel mediates OPIDN.A variety of OPs,exemplified by malathion,activates TRPA1 but not other neuronal TRP channels.Malathion increases the intracellular calcium levels and upregulates the excitability of mouse DRG neurons in vitro.Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors,which resembles the early symptoms of OPIDN.Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene.In the classic hens OPIDN model,malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate(TOCP),which also activates TRPA1 channel.Treatment with HC030031 reduces the damages caused by malathion or TOCP.Duloxetine and Ketotifen,two commercially available drugs exhibiting TRPA1 inhibitory activity,show neuroprotective effects against OPIDN and might be used in emergency situations.CONCLUSION TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.展开更多
Based on Kirchhoff plate theory and the Rayleigh-Ritz method,the model for free vibration of rectangular plate with rectangular cutouts under arbitrary elastic boundary conditions is established by using the improved ...Based on Kirchhoff plate theory and the Rayleigh-Ritz method,the model for free vibration of rectangular plate with rectangular cutouts under arbitrary elastic boundary conditions is established by using the improved Fourier series in combination with the independent coordinate coupling method(ICCM).The effect of the cutout is taken into account by subtracting the energies of the cutouts from the total energies of the whole plate.The vibration displacement function of the hole domain is based on the coordinate system of the hole domain in this method.From the continuity condition of the vibration displacement function at the cutout,the transition matrix between the two coordinate systems is constructed,and the mass and stiffness matrices are completely obtained.As a result,the calculation is simplified and the computational efficiency of the solution is improved.In this paper,numerical examples and modal experiments are presented to validate the effectiveness of the modeling methods,and parameters related to influencing factors of the rectangular plate are analyzed to study the vibration characteristics.展开更多
Northern China has rich wind power and photovoltaic renewable resources. Combined Heat and Power (CHP) Units to meet the load demand and limit its peaking capacity in winter, to a certain extent, it results in structu...Northern China has rich wind power and photovoltaic renewable resources. Combined Heat and Power (CHP) Units to meet the load demand and limit its peaking capacity in winter, to a certain extent, it results in structural problems of wind-solar power and thermoelectric. To solve these problems, this paper proposes a plurality of units together to ensure supply of heat load on the premise, by building a thermoelectric power peaking considering thermal load unit group dynamic scheduling model, to achieve the potential of different thermoelectric properties peaking units of the excavation. Simulation examples show, if the unit group exists obvious relationship thermoelectric individual differences, the thermal load dynamic scheduling can be more significantly improved overall performance peaking unit group, effectively increase clean energy consumptive.展开更多
A new type of magnesia spinel brick containing a novel flexibilizer was developed.The publication presents an investigation on its chemical composition,physical properties and cement clinker resistance.Compared to con...A new type of magnesia spinel brick containing a novel flexibilizer was developed.The publication presents an investigation on its chemical composition,physical properties and cement clinker resistance.Compared to conventional magnesia spinel bricks,the new brick type shows reduced amounts of alumina,significantly improved hot properties and resistance against cement clinker attack whilst keeping its textural flexibility on the same level.Field trials revealed satisfactory results and confirmed the novel flexibilizer concept.展开更多
Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion.However,the K-D-K-E catalytic motif of 2′-O-M...Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion.However,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to mammals.Here,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic center.We further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and SARS-CoV.These residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA substrates.Of interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral replication.Furthermore,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence pathogenesis.Monitoring changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.展开更多
In recent years, Combined electro-thermal system has developed rapidly. In order to provide the initial data for the analysis of the combined electro-thermal system, a practical energy flow calculation method for the ...In recent years, Combined electro-thermal system has developed rapidly. In order to provide the initial data for the analysis of the combined electro-thermal system, a practical energy flow calculation method for the combined electro-thermal system is proposed in this paper. Based on the detailed analysis of the topology structure of the heating network and its hydraulic and thermodynamic model, the forward-backward sweep method for the heat flow of the heating network is established, which is more suitable for the actual radial heating network. The electric and thermal coupling model for heating source, such as thermoelectric unit and electric boiler is established, and the heat flow of heating network and the power flow of power grid are calculated orderly, thus a fast calculation method for the combined electro-thermal system is formed. What’s more, a combined electro-thermal system with two-stage peak-shaving electric boiler is used as the example system. This paper validates the effectiveness and rapidity of this method through the example system, and analyzes the influence for the energy flow of combined electro-thermal system caused by the operating parameters such as the installation location of electric boiler, the outlet water temperature of heat source and the outlet flow rate, etc.展开更多
Short-term power flow analysis has a significant influence on day-ahead generation schedule. This paper proposes a time series model and prediction error distribution model of wind power output. With the consideration...Short-term power flow analysis has a significant influence on day-ahead generation schedule. This paper proposes a time series model and prediction error distribution model of wind power output. With the consideration of wind speed and wind power output forecast error’s correlation, the probabilistic distributions of transmission line flows during tomorrow’s 96 time intervals are obtained using cumulants combined Gram-Charlier expansion method. The probability density function and cumulative distribution function of transmission lines on each time interval could provide scheduling planners with more accurate and comprehensive information. Simulation in IEEE 39-bus system demonstrates effectiveness of the proposed model and algorithm.展开更多
The exploitation of a thin-layered reservoir with thickness less than 5 m(16 ft)needs to rely upon sedimentary facies analysis,due to the low resolution of seismic data and sparse well data.However,the ambiguity of fa...The exploitation of a thin-layered reservoir with thickness less than 5 m(16 ft)needs to rely upon sedimentary facies analysis,due to the low resolution of seismic data and sparse well data.However,the ambiguity of facies interpretation creates uncertainty in facies and reservoir mapping.The study aims to better define facies distribution,predict sand-body architecture,and consequently reduce risks in planning development wells,by integrating production data(dynamic)with conceptual geological models(static).An example is shown from the M1 Member of the Napo Formation in the B and G Oilfields(Block J),Oriente Basin,Ecuador.The M1 reservoir is a thin-layered sandstone reservoir below seismic resolution.Core and well-log facies interpretation indicates depositional facies of a tidedominated estuary.Production data during the water injection phase of field development can delineate the detailed geometry of the sand bodies.The injector-producer rate responses can determine the connectivity of sand bodies.Well performance during primary recovery can capture the scale of single reservoirs because the initial production rates and the cumulative oil production of individual wells are generally proportional to the size of sand bodies.A facies model was thereby generated.Two step-out wells were planned using this model and drilled successfully.The results demonstrate that the integration of dynamic and static data is critical to understanding reservoir facies distribution.展开更多
Despite the availability of vaccines and antiviral treatments,the continued emergence of severe acute respira-tory syndrome coronavirus 2(SARS-CoV-2)variants and breakthrough infections underscores the need for new,po...Despite the availability of vaccines and antiviral treatments,the continued emergence of severe acute respira-tory syndrome coronavirus 2(SARS-CoV-2)variants and breakthrough infections underscores the need for new,potent antiviral therapies.In a previous study,we established a transcription and replication-competent SARS-CoV-2 virus-like particle(trVLP)system that recapitulates the complete viral life cycle.In this study,we combined high-content screening(HCS)with the SARS-CoV-2 trVLP cell culture system,providing a powerful phenotype-oriented approach to assess the antiviral potential of compounds on a large scale.We screened a library of 3,200 natural compounds and identified drupacine as a potential candidate against SARS-CoV-2 infection.Furthermore,we utilized a SARS-CoV-2 replicon system to demonstrate that drupacine could inhibit viral genome transcription and replication.However,in vitro,enzymatic assays revealed that the inhibition could not be attributed to conventional antiviral targets,such as the viral non-structural proteins nsp5(MPro)or nsp12(RdRp).In conclusion,our findings position drupacine as a promising antiviral candidate against SARS-CoV-2,providing a novel scaffold for developing anti-coronavirus disease 2019 therapeutics.Further investigation is required to pinpoint its precise target and mechanism of action.展开更多
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University scheme of the Ministry of Education of China(NO.IRT1111)the National Basic Research Program of China(2012CB518300)+2 种基金the National Natural Science Foundation of China(81101946)the Shanghai Pujiang Program(12PJD008)Prostate Cancer Foundation Young Investigator Award,Shanghai Municipal Health and Family Planning Commission Outstanding Young Investigator(XYQ2013077).
文摘The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.
基金supported in part by the National Natural Science Foundation of China(No.81071753)
文摘Hypoxia-induced factor-1 alpha (HIF-1α) affects many effector molecules and regulates tumor lymphangio- genesis and angiogenesis during hypoxia. The aim of this study was to investigate the role of HIF-1α in the regu- lation of vascular endothelial growth factor C (VEGF-C) expression and its effect on lymphangiogenesis and an- giogenesis in breast cancer. Lymphatic vessel density (LVD), microvessel density (MVD) and the expressions of HIF-1α and VEGF-C proteins were evaluated by immunohistochemistry in 75 breast cancer samples. There was a significant correlation between HIF-1α and VEGF-C (P = 0.014, r = 0.273, Spearman's coefficient of correlation). HIF-1α and VEGF-C overexpression was significantly correlated with higher LVD (P = 0.003 and P = 0.017, re- spectively), regional lymph nodal involvement (P = 0.002 and P = 0.004, respectively) and advanced tumor, node, metastasis (TNM) classification (P = 0.001 and P = 0.01, respectively). Higher MVD was observed in the group expressing higher levels of HIF-1α and VEGF-C (P = 0.033 and P = 0.037, respectively). Univariate analysis showed shorter survival time in patients expressing higher levels of HIF-1α and VEGF-C. HIF-1α was also found to be an independent prognostic factor of overall survival in multivariate analysis. The results suggest that HIF-1α may affect VEGF-C expression, thus acting as a crucial regulator of lymphangiogenesis and angiogenesis in breast cancer. This study highlights promising potential of HIF- 1α as a therapeutic target against tumor lymph node me- tastasis.
文摘We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro.The capacities for mammosphere formation and STAT3 expression of CD44+CD24-/low MCF-7 and MCF-7 were observed.The CD44+CD24-/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant(TAM-R) cells.Cell cycle,apoptosis,STAT3 and phospho-STAT3 changes were observed af-ter treatment with tamoxifen.Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed.CD44+CD24-/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7.The CD44+CD24-/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7.Cell cycle changes,anti-apoptotic effects and STAT3 changes were also found.Mean-while,the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen.It is concluded that STAT3 plays an essential role in breast cancer stem cells,which correlated with tamoxifen resistance.
基金the financial support provided by the National Key Research and Development Program of China(2016YFA0203600)the Natural Science Foundation of China(NSFC)Project(31822019,51703195,91859116,81430040,81571738)+4 种基金the One Belt and One Road International Cooperation Project from Key Research and Development Program of Zhejiang Province(2019C04024)the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”,China(2018ZX09711002)the Zhejiang Provincial Natural Science Foundation of China(LGF19C100002)the Fundamental Research Funds for the Central Universities(2019XZZX00415,2020FZZX001-05)the Leading Talent of“Ten Thousand Plan”-National High-Level Talents Special Support Plan。
文摘Simultaneous photothermal therapy(PTT)and photodynamic therapy(PDT)is beneficial for enhanced cancer therapy due to the synergistic effect.Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources.The emerging monocomponent diketopyrrolopyrrole(DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation,but suffer from low singlet oxygen quantum yield,which severely restricts the therapeutic efficacy.Herein,we report acceptor-oriented molecular design of a donor-acceptor-donor(D-A-D)conjugated small molecule(IID-ThTPA)-based phototheranostic agent,with isoindigo(IID)as selective acceptor and triphenylamine(TPA)as donor.The strong D-A strength and narrow singlet-triplet energy gap endow IID-ThTPA nanoparticles(IID-ThTPA NPs)high mass extinction coefficient(18.2 L g^-1 cm^-1),competitive photothermal conversion efficiency(35.4%),and a dramatically enhanced singlet oxygen quantum yield(84.0%)comparing with previously reported monocomponent PTT/PDT agents.Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.
基金the financial support from the China Scholarship Councilthe Natural Sciences and the Engineering Research Council (NSRC) of Canada
文摘Dropshafts are vertical structures widely used in urban drainage systems and buildings for water transportation.In this paper,a physical model study was conducted to investigate the air entrainment in the dropshaft under various flow regimes with and without air ventilation.Observed from the experiments,the air entrainment mechanisms varied with the water flow regimes in the dropshaft.When there was no water plug formed in the dropshaft,air could be supplied directly from downstream.Once the water plug was formed,while without venting,the air was replenished only from downstream intermittently and then in the form of large air bubble traveling upwards to the airspace at the top;while with venting,air was mainly replenished from the dropshaft top and no large air bubble was observed.The experimental results also showed that the amount of entrained air in the dropshaft with venting was greater than that without venting.
基金supported by National Key Scientific Instrument&Equipment Development Program of China(2012YQ03026010)the Joint NSFC-ISF Research Program(8146114802)+2 种基金jointly funded by the National Natural Science Foundation of China and the Israel Science Foundationthe State Key Program of Basic Research of China(2013CB910604)the National Natural Science Foundation of China(61327014 and 61175103)
文摘OBJECTIVE We want to investigate the mechanism of organophosphate-induced delayed neuropathy(OPIDN) and find appropriate therapeutic medicine.OPIDN,often leads to paresthesias,ataxia and paralysis,occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate(OP) insecticides or nerve agents,and may contribute to the Gulf War Syndrome.METHODS FDSS Ca2^(+)-influx assays,single-cell calcium imaging and patch-clamp electrophysiology were the major testing techniques.Transfected HEK293 cells and dorsal root ganglion(DRG) neurons were used to evaluate the effects of compounds.Wild type and trpa1 knockout mice and adult hyline brown hens were used to evaluate the neuropathological damages caused by the OPs.Transmission electron microscopy imaging was used to observe the nerve injuries ultrastructurally.High-throughput screen for TRPA1 inhibitors was accomplished by Ion Works Barracuda(IWB) automated electrophysiology assay.RESULTS TRPA1(Transient receptor potential cation channel,member A1) channel mediates OPIDN.A variety of OPs,exemplified by malathion,activates TRPA1 but not other neuronal TRP channels.Malathion increases the intracellular calcium levels and upregulates the excitability of mouse DRG neurons in vitro.Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors,which resembles the early symptoms of OPIDN.Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene.In the classic hens OPIDN model,malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate(TOCP),which also activates TRPA1 channel.Treatment with HC030031 reduces the damages caused by malathion or TOCP.Duloxetine and Ketotifen,two commercially available drugs exhibiting TRPA1 inhibitory activity,show neuroprotective effects against OPIDN and might be used in emergency situations.CONCLUSION TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.
基金support of this work by the National Natural Science Foundation of China(No.51405096)the Fundamental Research Funds for the Central Universities(HEUCF210710).
文摘Based on Kirchhoff plate theory and the Rayleigh-Ritz method,the model for free vibration of rectangular plate with rectangular cutouts under arbitrary elastic boundary conditions is established by using the improved Fourier series in combination with the independent coordinate coupling method(ICCM).The effect of the cutout is taken into account by subtracting the energies of the cutouts from the total energies of the whole plate.The vibration displacement function of the hole domain is based on the coordinate system of the hole domain in this method.From the continuity condition of the vibration displacement function at the cutout,the transition matrix between the two coordinate systems is constructed,and the mass and stiffness matrices are completely obtained.As a result,the calculation is simplified and the computational efficiency of the solution is improved.In this paper,numerical examples and modal experiments are presented to validate the effectiveness of the modeling methods,and parameters related to influencing factors of the rectangular plate are analyzed to study the vibration characteristics.
文摘Northern China has rich wind power and photovoltaic renewable resources. Combined Heat and Power (CHP) Units to meet the load demand and limit its peaking capacity in winter, to a certain extent, it results in structural problems of wind-solar power and thermoelectric. To solve these problems, this paper proposes a plurality of units together to ensure supply of heat load on the premise, by building a thermoelectric power peaking considering thermal load unit group dynamic scheduling model, to achieve the potential of different thermoelectric properties peaking units of the excavation. Simulation examples show, if the unit group exists obvious relationship thermoelectric individual differences, the thermal load dynamic scheduling can be more significantly improved overall performance peaking unit group, effectively increase clean energy consumptive.
文摘A new type of magnesia spinel brick containing a novel flexibilizer was developed.The publication presents an investigation on its chemical composition,physical properties and cement clinker resistance.Compared to conventional magnesia spinel bricks,the new brick type shows reduced amounts of alumina,significantly improved hot properties and resistance against cement clinker attack whilst keeping its textural flexibility on the same level.Field trials revealed satisfactory results and confirmed the novel flexibilizer concept.
基金partially sponsored by contributions from the National Key R&D Program of China(2021YFA1300800)the China NSFC projects(82172243,82341061,and 82372223)the Fundamental Research Funds for Central Universities(2042023kf1028 and 2042022dx0003).
文摘Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion.However,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to mammals.Here,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic center.We further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and SARS-CoV.These residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA substrates.Of interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral replication.Furthermore,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence pathogenesis.Monitoring changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.
文摘In recent years, Combined electro-thermal system has developed rapidly. In order to provide the initial data for the analysis of the combined electro-thermal system, a practical energy flow calculation method for the combined electro-thermal system is proposed in this paper. Based on the detailed analysis of the topology structure of the heating network and its hydraulic and thermodynamic model, the forward-backward sweep method for the heat flow of the heating network is established, which is more suitable for the actual radial heating network. The electric and thermal coupling model for heating source, such as thermoelectric unit and electric boiler is established, and the heat flow of heating network and the power flow of power grid are calculated orderly, thus a fast calculation method for the combined electro-thermal system is formed. What’s more, a combined electro-thermal system with two-stage peak-shaving electric boiler is used as the example system. This paper validates the effectiveness and rapidity of this method through the example system, and analyzes the influence for the energy flow of combined electro-thermal system caused by the operating parameters such as the installation location of electric boiler, the outlet water temperature of heat source and the outlet flow rate, etc.
文摘Short-term power flow analysis has a significant influence on day-ahead generation schedule. This paper proposes a time series model and prediction error distribution model of wind power output. With the consideration of wind speed and wind power output forecast error’s correlation, the probabilistic distributions of transmission line flows during tomorrow’s 96 time intervals are obtained using cumulants combined Gram-Charlier expansion method. The probability density function and cumulative distribution function of transmission lines on each time interval could provide scheduling planners with more accurate and comprehensive information. Simulation in IEEE 39-bus system demonstrates effectiveness of the proposed model and algorithm.
基金the China National Science and Technology Major Project(No.2016ZX05002-006).
文摘The exploitation of a thin-layered reservoir with thickness less than 5 m(16 ft)needs to rely upon sedimentary facies analysis,due to the low resolution of seismic data and sparse well data.However,the ambiguity of facies interpretation creates uncertainty in facies and reservoir mapping.The study aims to better define facies distribution,predict sand-body architecture,and consequently reduce risks in planning development wells,by integrating production data(dynamic)with conceptual geological models(static).An example is shown from the M1 Member of the Napo Formation in the B and G Oilfields(Block J),Oriente Basin,Ecuador.The M1 reservoir is a thin-layered sandstone reservoir below seismic resolution.Core and well-log facies interpretation indicates depositional facies of a tidedominated estuary.Production data during the water injection phase of field development can delineate the detailed geometry of the sand bodies.The injector-producer rate responses can determine the connectivity of sand bodies.Well performance during primary recovery can capture the scale of single reservoirs because the initial production rates and the cumulative oil production of individual wells are generally proportional to the size of sand bodies.A facies model was thereby generated.Two step-out wells were planned using this model and drilled successfully.The results demonstrate that the integration of dynamic and static data is critical to understanding reservoir facies distribution.
基金supported by the National Natural Science Foundation of China(82341084,82241077,82272302,and 32070153)National Key Research and Development Plan of China(2023YFC2305900 and 2021YFC2300200-04)Tsinghua University Dushi Program(20231080039)。
文摘Despite the availability of vaccines and antiviral treatments,the continued emergence of severe acute respira-tory syndrome coronavirus 2(SARS-CoV-2)variants and breakthrough infections underscores the need for new,potent antiviral therapies.In a previous study,we established a transcription and replication-competent SARS-CoV-2 virus-like particle(trVLP)system that recapitulates the complete viral life cycle.In this study,we combined high-content screening(HCS)with the SARS-CoV-2 trVLP cell culture system,providing a powerful phenotype-oriented approach to assess the antiviral potential of compounds on a large scale.We screened a library of 3,200 natural compounds and identified drupacine as a potential candidate against SARS-CoV-2 infection.Furthermore,we utilized a SARS-CoV-2 replicon system to demonstrate that drupacine could inhibit viral genome transcription and replication.However,in vitro,enzymatic assays revealed that the inhibition could not be attributed to conventional antiviral targets,such as the viral non-structural proteins nsp5(MPro)or nsp12(RdRp).In conclusion,our findings position drupacine as a promising antiviral candidate against SARS-CoV-2,providing a novel scaffold for developing anti-coronavirus disease 2019 therapeutics.Further investigation is required to pinpoint its precise target and mechanism of action.