The Earth’s Free Core Nutation(FCN) causes Earth tides and forced nutation with frequencies close to the FCN that exhibit resonance effects.High-precision superconducting gravimeter(SG) and very long baseline interfe...The Earth’s Free Core Nutation(FCN) causes Earth tides and forced nutation with frequencies close to the FCN that exhibit resonance effects.High-precision superconducting gravimeter(SG) and very long baseline interferometry(VLBI) provide good observation techniques for detecting the FCN parameters.However,some choices in data processing and solution procedures increase the uncertainty of the FCN parameters.In this study,we analyzed the differences and the effectiveness of weight function and ocean tide corrections in the FCN parameter detection using synthetic data,SG data from thirty-one stations,and the 10 celestial pole offset(CPO) series.The results show that significant discrepancies are caused by different computing options for a single SG station.The stacking method,which results in a variation of0.24-5 sidereal days(SDs) in the FCN period(T) and 10^(3)-10^(4) in the quality factor(Q) due to the selection of the weighting function and the ocean tide model(OTM),can effectively suppress this influence.The statistical analysis results of synthetic data shows that although different weight choices,while adjusting the proportion of diurnal tidal waves involved,do not significantly improve the accuracy of fitted FCN parameters from gravity observations.The study evaluated a series of OTMs using the loading correction efficiency.The fitting of FCN parameters can be improved by selecting the mean of appropriate OTMs based on the evaluation results.Through the estimation of the FCN parameters based on the forced nutation,it was found that the weight function P_(1) is more suitable than others,and different CPO series(after 2009) resulted in a difference of 0.4 SDs in the T and of 103 in the Q.We estimated the FCN parameters for SG(T=430.4±1.5 SDs and Q=1.52×10^(4)±2.5×10^(3)) and for VLBI(T=429.8±0.7 SDs,Q=1.88×10^(4)±2.1×10^(3)).展开更多
Tight conglomerate reservoirs are featured with extremely low permeability,strong heterogeneity and poor water injectivity.CO_(2) huff-n-puff has been considered a promising candidate to enhance oil recovery in tight ...Tight conglomerate reservoirs are featured with extremely low permeability,strong heterogeneity and poor water injectivity.CO_(2) huff-n-puff has been considered a promising candidate to enhance oil recovery in tight reservoirs,owing to its advantages in reducing oil viscosity,improving mobility ratio,quickly replenishing formation pressure,and potentially achieving a miscible state.However,reliable inhouse laboratory evaluation of CO_(2) huff-n-puff in natural conglomerate cores is challenging due to the inherent high formation pressure.In this study,we put forward an equivalent method based on the similarity of the miscibility index and Grashof number to acquire a lab-controllable pressure that features the flow characteristics of CO_(2) injection in a tight conglomerate reservoir.The impacts of depletion degree,pore volume injection of CO_(2) and soaking time on ultimate oil recovery in tight cores from the Mahu conglomerate reservoir were successfully tested at an equivalent pressure.Our results showed that oil recovery decreased with increased depletion degree while exhibiting a non-monotonic tendency(first increased and then decreased)with increased CO_(2) injection volume and soaking time.The lower oil recoveries under excess CO_(2) injection and soaking time were attributed to limited CO_(2) dissolution and asphaltene precipitation.This work guides secure and reliable laboratory design of CO_(2) huff-n-puff in tight reservoirs with high formation pressure.展开更多
The 3D visualization of the porosity in high-pressure die casting(HPDC)Mg alloys AZ91D and Mg4Ce2Al0.5Mn(EA42)was investigated by X-ray computed tomography.It was demonstrated that the volumetric porosity at the near-...The 3D visualization of the porosity in high-pressure die casting(HPDC)Mg alloys AZ91D and Mg4Ce2Al0.5Mn(EA42)was investigated by X-ray computed tomography.It was demonstrated that the volumetric porosity at the near-gate location for alloy EA42 was significantly higher than that far from the gate location.This difference resulted from the low valid time during intensified casting pressure conditions.Specimens of alloy EA42 exhibited a narrow pore distribution in the side view(~0.5 mm)compared to the wide distribution(~1.8 mm)of alloy AZ91D,which was mainly attributed to the formation mechanism of the defect band.The formation of microporosity in the defect band of alloy EA42 was inhibited because of the significant latent heat released by a large amount of the Al11Ce3phase segregated in the defect band during solidification.Additionally,an effective estimator(Z-Propagation)was introduced,which is proposed to predict the projected area fraction of the porosity(f)involved during tensile failure with better effectiveness compared with traditional methods based on the actual fractured surface.By coupling the Z-Propagation method with the critical local strain model,the logarithmic fracture strain and true fracture stress of the specimens were predicted within 3.03%and 1.65%of the absolute value of the average relative error(AARE),respectively.展开更多
Crystallization in supersaturated solution plays a fundamental role in a variety of natural and industrial processes.However,a thorough understanding of crystallization phenomena in supersaturated solution is still di...Crystallization in supersaturated solution plays a fundamental role in a variety of natural and industrial processes.However,a thorough understanding of crystallization phenomena in supersaturated solution is still difficult because the real-time visualization of crystallization processes under supersaturated condition is a great challenge.Herein,an electron beam-induced crystallization method was carried out in in situ liquid cell transmission electron microscopy(TEM)to visualize the crystallization of NaCl under supersaturated condition in real time.Crucial steps and behaviors in the crystallization of NaCl were captured and clarified,including the growth of NaCl nanocrystals with different morphologies,the formation of initial crystalline seeds from amorphous ion clusters,and the non-equilibrium growth behaviors caused by uneven distribution of precursor ions.This study provides the real-time visualization of detailed nucleation and growth behaviors in NaCl crystallization and brings an ideal strategy for investigating crystallization phenomena under supersaturated condition.展开更多
Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable,as they could prevent the invading pathogens at their initial infection sites in a convenient and userfriendly way. Nanovaccines...Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable,as they could prevent the invading pathogens at their initial infection sites in a convenient and userfriendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens.Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.展开更多
The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictab...The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.展开更多
Analysis of complementarity determining region 3 （CDR3） length of T lymphocyte receptors （TCRs） by immunoscope spectratyping technique has been used successfully to investigate the diversity of TCR in autoimmune d...Analysis of complementarity determining region 3 （CDR3） length of T lymphocyte receptors （TCRs） by immunoscope spectratyping technique has been used successfully to investigate the diversity of TCR in autoimmune diseases and infection diseases. In this study, we investigated the patterns of CDR3 length distribution for all 32 TCR AV gene families in human peripheral blood lymphocytes of four normal volunteers by the immunoscope spectratyping technique. It was found that PCR products exhibited an obscure band on 1.5% agarose gel electrophoresis. Each TCR AV family exhibited more than 8 bands on 6% sequencing gel electrophoresis. The CDR3 spectratyping of all TCR AV families showed a standard Gaussian distribution with different CDR3 length, and the expression frequency of CDR3 was similar among the gene families. Most of CDR3 in TCR AV family recombine in frame. However, some of the CDR3 showed out-of frame gene rearrangement. Additionally, we found that in some of TCR AV families there were 18 amino acid discrepancies between the longest CDR3 and shortest CDR3. These results may be helpful to further study the recombination mechanism of human TCR genes, the TCR CDR3 gene repertoire, and the repertoire drift in health people and disease state. Cellular ＆ Molecular Immunology.展开更多
Coronaviruses(CoVs)are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome(SARS)and Middle East Respiratory Syndrome(MERS).Severe...Coronaviruses(CoVs)are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome(SARS)and Middle East Respiratory Syndrome(MERS).Severe Acute Respiratory Syndrome coronavirus 2(SARS-CoV-2)disease(COVID-19)has caused major public health crises.There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date(16/05/2020).SARS-CoV,MERSCoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity.To date,there is no specific treatment proven effective against these viral infectious diseases.Vaccination is considered one of the most effective strategies to prevent viral infections.Therefore,the development of effective vaccines against highly pathogenic coronaviruses is essential.In this review,we will briefly describe coronavirus vaccine design targets,summarize recent advances in the development of coronavirus vaccines,and highlight current adjuvants for improving the efficacy of coronavirus vaccines.展开更多
Cystathionine-γ-lyase(CSE),an enzyme associated with hydrogen sulfide(H2S)production,is an important endogenous regulator of inflammation.Jumonji domain-containing protein 3(JMJD3)is implicated in the immune response...Cystathionine-γ-lyase(CSE),an enzyme associated with hydrogen sulfide(H2S)production,is an important endogenous regulator of inflammation.Jumonji domain-containing protein 3(JMJD3)is implicated in the immune response and inflammation.Here,we investigated the potential contribution of JMJD3 to endogenous CSE-mediated inflammation in rheumatoid arthritis(RA).Upregulated CSE and JMJD3 were identified in synovial fibroblasts(SFs)from RA patients as well as in the joints of arthritic mice.Knocking down CSE augmented inflammation in IL-1β-induced SFs by increasing JMJD3 expression.In addition,CSE−/−mice with collagen-induced arthritis(CIA)developed severe joint inflammation and bone erosion.Conversely,overexpressing CSE inhibited JMJD3 expression by the transcription factor Sp-1 and was accompanied by reduced inflammation in IL-1β-treated SFs.Furthermore,JMJD3 silencing or the administration of the JMJD3 inhibitor GSK-J4 significantly decreased the inflammatory response in IL-1β-treated SFs,mainly by controlling the methylation status of H3K27me3 at the promoter of its target genes.GSK-J4 markedly attenuated the severity of arthritis in CIA mice.In conclusion,suppressing JMJD3 expression by the transcription factor Sp-1 is likely responsible for the ability of CSE to negatively modulate the inflammatory response and reduce the progression of RA.展开更多
基金supported by the Open Fund of Hubei Luojia Laboratory (No. 220100033)the Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDB41000000)+1 种基金National Natural Science Foundation of China (Grant Nos. 42174108, 41874094, 42192535 and 42242015)the Young Top-notch Talent Cultivation Program of Hubei Province。
文摘The Earth’s Free Core Nutation(FCN) causes Earth tides and forced nutation with frequencies close to the FCN that exhibit resonance effects.High-precision superconducting gravimeter(SG) and very long baseline interferometry(VLBI) provide good observation techniques for detecting the FCN parameters.However,some choices in data processing and solution procedures increase the uncertainty of the FCN parameters.In this study,we analyzed the differences and the effectiveness of weight function and ocean tide corrections in the FCN parameter detection using synthetic data,SG data from thirty-one stations,and the 10 celestial pole offset(CPO) series.The results show that significant discrepancies are caused by different computing options for a single SG station.The stacking method,which results in a variation of0.24-5 sidereal days(SDs) in the FCN period(T) and 10^(3)-10^(4) in the quality factor(Q) due to the selection of the weighting function and the ocean tide model(OTM),can effectively suppress this influence.The statistical analysis results of synthetic data shows that although different weight choices,while adjusting the proportion of diurnal tidal waves involved,do not significantly improve the accuracy of fitted FCN parameters from gravity observations.The study evaluated a series of OTMs using the loading correction efficiency.The fitting of FCN parameters can be improved by selecting the mean of appropriate OTMs based on the evaluation results.Through the estimation of the FCN parameters based on the forced nutation,it was found that the weight function P_(1) is more suitable than others,and different CPO series(after 2009) resulted in a difference of 0.4 SDs in the T and of 103 in the Q.We estimated the FCN parameters for SG(T=430.4±1.5 SDs and Q=1.52×10^(4)±2.5×10^(3)) and for VLBI(T=429.8±0.7 SDs,Q=1.88×10^(4)±2.1×10^(3)).
基金This study is financially supported by CNPC Innovation Foundation(2020D-5007-0214)Major Strategic Project of CNPC(ZLZX2020-01-04)Beijing Municipal Excellent Talent Training Funds Youth Advanced Individual Project(2018000020124G163)。
文摘Tight conglomerate reservoirs are featured with extremely low permeability,strong heterogeneity and poor water injectivity.CO_(2) huff-n-puff has been considered a promising candidate to enhance oil recovery in tight reservoirs,owing to its advantages in reducing oil viscosity,improving mobility ratio,quickly replenishing formation pressure,and potentially achieving a miscible state.However,reliable inhouse laboratory evaluation of CO_(2) huff-n-puff in natural conglomerate cores is challenging due to the inherent high formation pressure.In this study,we put forward an equivalent method based on the similarity of the miscibility index and Grashof number to acquire a lab-controllable pressure that features the flow characteristics of CO_(2) injection in a tight conglomerate reservoir.The impacts of depletion degree,pore volume injection of CO_(2) and soaking time on ultimate oil recovery in tight cores from the Mahu conglomerate reservoir were successfully tested at an equivalent pressure.Our results showed that oil recovery decreased with increased depletion degree while exhibiting a non-monotonic tendency(first increased and then decreased)with increased CO_(2) injection volume and soaking time.The lower oil recoveries under excess CO_(2) injection and soaking time were attributed to limited CO_(2) dissolution and asphaltene precipitation.This work guides secure and reliable laboratory design of CO_(2) huff-n-puff in tight reservoirs with high formation pressure.
基金financially the Major Science and Technology projects in Qinghai province(2018GX-A1)Shanghai Science and Technology Committee(No.18511109302)+1 种基金The National Key R&D Program(No.2016YFB0301002)the Ministry of Science and Technology of Chinaco-funded by the National Natural Science Foundation of China(No.51825101)。
文摘The 3D visualization of the porosity in high-pressure die casting(HPDC)Mg alloys AZ91D and Mg4Ce2Al0.5Mn(EA42)was investigated by X-ray computed tomography.It was demonstrated that the volumetric porosity at the near-gate location for alloy EA42 was significantly higher than that far from the gate location.This difference resulted from the low valid time during intensified casting pressure conditions.Specimens of alloy EA42 exhibited a narrow pore distribution in the side view(~0.5 mm)compared to the wide distribution(~1.8 mm)of alloy AZ91D,which was mainly attributed to the formation mechanism of the defect band.The formation of microporosity in the defect band of alloy EA42 was inhibited because of the significant latent heat released by a large amount of the Al11Ce3phase segregated in the defect band during solidification.Additionally,an effective estimator(Z-Propagation)was introduced,which is proposed to predict the projected area fraction of the porosity(f)involved during tensile failure with better effectiveness compared with traditional methods based on the actual fractured surface.By coupling the Z-Propagation method with the critical local strain model,the logarithmic fracture strain and true fracture stress of the specimens were predicted within 3.03%and 1.65%of the absolute value of the average relative error(AARE),respectively.
基金supported by the National Natural Science Foundation of China(Nos.61974021 and 12234005)New Cornerstone Science Foundation and XPLORER PRIZE,and the Fundamental Research Funds for the Central Universities.
文摘Crystallization in supersaturated solution plays a fundamental role in a variety of natural and industrial processes.However,a thorough understanding of crystallization phenomena in supersaturated solution is still difficult because the real-time visualization of crystallization processes under supersaturated condition is a great challenge.Herein,an electron beam-induced crystallization method was carried out in in situ liquid cell transmission electron microscopy(TEM)to visualize the crystallization of NaCl under supersaturated condition in real time.Crucial steps and behaviors in the crystallization of NaCl were captured and clarified,including the growth of NaCl nanocrystals with different morphologies,the formation of initial crystalline seeds from amorphous ion clusters,and the non-equilibrium growth behaviors caused by uneven distribution of precursor ions.This study provides the real-time visualization of detailed nucleation and growth behaviors in NaCl crystallization and brings an ideal strategy for investigating crystallization phenomena under supersaturated condition.
基金supported by National Natural Science Foundation of China (Grant Nos. 81925036 & 82003684)China Postdoctoral Science Foundation Grant (2019M663534, China)+3 种基金the Key Research and Development Program of Science and Technology Department of Sichuan Province (No. 2020YFS0570, China)Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (CARS-SVDIP, China)the Fundamental Research Funds for the Central UniversitiesSichuan University Postdoctoral Interdisciplinary Innovation Fund。
文摘Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable,as they could prevent the invading pathogens at their initial infection sites in a convenient and userfriendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens.Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.
基金financially supported by the National Natural Science Foundation of China(81925036&81872814)the Key Research and Development Program of Science and Technology Department of Sichuan Province(2020YFS0570,China)+2 种基金Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(CARS-SVDIP)111 project(b18035,China)the Fundamental Research Funds for the Central Universities(China)。
文摘The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.
文摘Analysis of complementarity determining region 3 （CDR3） length of T lymphocyte receptors （TCRs） by immunoscope spectratyping technique has been used successfully to investigate the diversity of TCR in autoimmune diseases and infection diseases. In this study, we investigated the patterns of CDR3 length distribution for all 32 TCR AV gene families in human peripheral blood lymphocytes of four normal volunteers by the immunoscope spectratyping technique. It was found that PCR products exhibited an obscure band on 1.5% agarose gel electrophoresis. Each TCR AV family exhibited more than 8 bands on 6% sequencing gel electrophoresis. The CDR3 spectratyping of all TCR AV families showed a standard Gaussian distribution with different CDR3 length, and the expression frequency of CDR3 was similar among the gene families. Most of CDR3 in TCR AV family recombine in frame. However, some of the CDR3 showed out-of frame gene rearrangement. Additionally, we found that in some of TCR AV families there were 18 amino acid discrepancies between the longest CDR3 and shortest CDR3. These results may be helpful to further study the recombination mechanism of human TCR genes, the TCR CDR3 gene repertoire, and the repertoire drift in health people and disease state. Cellular ＆ Molecular Immunology.
基金financial support of the National Natural Science Foundation of China(No.81925036)Special Funds for Prevention and Control of COVID-19 of Sichuan University(No.0082604151018,China)Zhejiang University special scientific research fund for COVID-19 prevention and control(No.2020XG2X018,China)
文摘Coronaviruses(CoVs)are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome(SARS)and Middle East Respiratory Syndrome(MERS).Severe Acute Respiratory Syndrome coronavirus 2(SARS-CoV-2)disease(COVID-19)has caused major public health crises.There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date(16/05/2020).SARS-CoV,MERSCoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity.To date,there is no specific treatment proven effective against these viral infectious diseases.Vaccination is considered one of the most effective strategies to prevent viral infections.Therefore,the development of effective vaccines against highly pathogenic coronaviruses is essential.In this review,we will briefly describe coronavirus vaccine design targets,summarize recent advances in the development of coronavirus vaccines,and highlight current adjuvants for improving the efficacy of coronavirus vaccines.
基金supported by grants from National Natural Science Foundation of China(No.8167342881330080)a key laboratory program of the Education Commission of Shanghai Municipality(No.ZDSYS14005).
文摘Cystathionine-γ-lyase(CSE),an enzyme associated with hydrogen sulfide(H2S)production,is an important endogenous regulator of inflammation.Jumonji domain-containing protein 3(JMJD3)is implicated in the immune response and inflammation.Here,we investigated the potential contribution of JMJD3 to endogenous CSE-mediated inflammation in rheumatoid arthritis(RA).Upregulated CSE and JMJD3 were identified in synovial fibroblasts(SFs)from RA patients as well as in the joints of arthritic mice.Knocking down CSE augmented inflammation in IL-1β-induced SFs by increasing JMJD3 expression.In addition,CSE−/−mice with collagen-induced arthritis(CIA)developed severe joint inflammation and bone erosion.Conversely,overexpressing CSE inhibited JMJD3 expression by the transcription factor Sp-1 and was accompanied by reduced inflammation in IL-1β-treated SFs.Furthermore,JMJD3 silencing or the administration of the JMJD3 inhibitor GSK-J4 significantly decreased the inflammatory response in IL-1β-treated SFs,mainly by controlling the methylation status of H3K27me3 at the promoter of its target genes.GSK-J4 markedly attenuated the severity of arthritis in CIA mice.In conclusion,suppressing JMJD3 expression by the transcription factor Sp-1 is likely responsible for the ability of CSE to negatively modulate the inflammatory response and reduce the progression of RA.
