The stability of slopes is essential for ensuring safe production in open-pit mines.Analyzing and managing the deformation and failure of the slope rock mass becomes more challenging as the slope height increases.To i...The stability of slopes is essential for ensuring safe production in open-pit mines.Analyzing and managing the deformation and failure of the slope rock mass becomes more challenging as the slope height increases.To investigate the damage patterns of slopes with varying heights,three slope models were developed based on a rock slope in Dagushan,China.The deformation failure processes of slopes under the influence of excavation and unloading were analyzed using the base friction test method in combination with digital image technology contrasting.The results supported the following findings:(1)Unloading tensile stress caused lateral partitioning in the slope.Both the foot and top of the slope underwent initial tensile cracks.(2)The destabilization mechanism of unloading deformation in slopes of different heights involved a combination of traction at the foot of the slope or pushing at the top of the slope,followed by accelerated deformation,deceleration creep,and overall destabilization.(3)The unloading damage patterns of slopes at different heights were summarized as follows:compression tension cracking,traction,and slip damage for medium and low slopes;compression tension cracking,traction,and slip failure for the upper part of high slopes;and relaxation tension cracking,pushing,traction,and slip failure for the lower part.Moreover,the upper part of ultra-high slopes exhibited compression tension cracking,traction,and slip failure,while the middle and lower parts displayed relaxation tension cracking,pushing,traction,and slip patterns.Finally,numerical simulations were conducted to verify the results of the test analyses,which demonstrated good consistency.These research results were of great engineering value for proposing effective safety management measures for high slopes.展开更多
Through on-site defect investigation,special inspection,and finite element simulation calculation of a high-speed upper-span(30+32+30)m prestressed concrete box girder bridge,the overall sliding force of the bridge on...Through on-site defect investigation,special inspection,and finite element simulation calculation of a high-speed upper-span(30+32+30)m prestressed concrete box girder bridge,the overall sliding force of the bridge on the right side of platform 0#is analyzed.In this situation,typical defects such as overall girder slippage,support dislocation,pier column deviation,and pier bottom side cracks have occurred in the overpass.At the same time,combined with simulation calculation analysis,it is interpreted that the 0#and 1#foundation has been damaged at a certain position below the ground line.The occurrence of broken piles has provided a reliable basis for the later reinforcement and maintenance of the bridge and ideas for emergency inspection and analysis of bridges damaged by the same type of landslides.展开更多
BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatme...BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.展开更多
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related ...The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.展开更多
All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecul...All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.展开更多
Liquefaction of sandy soils is a big threat to the stability and the safety of an earth embankment laid on saturated soils.A large number of liquefaction-induced damages on embankment due to different types of earthqu...Liquefaction of sandy soils is a big threat to the stability and the safety of an earth embankment laid on saturated soils.A large number of liquefaction-induced damages on embankment due to different types of earthquakes have been reported worldwide.In this research,the dynamic behaviors of earth embankment and the reinforcement effects of grouting as remediation method,subjected to moderate earthquake EQ1 and strong earthquake EQ2,were numerically investigated.The seismic behaviors of ground composed of cohesionless sandy soil and cohesive clayey soil were uniformly described by the cyclic mobility(CM)model,which is capable of describing accurately the mechanical property of the soil due to monotonic and cyclic loadings by accounting for stress-induced anisotropy,over-consolidation,and soil structure.It is known from the numerical investigation that the embankment would experience destructive deformation,and that the collapse mode was closely related to the properties of input seismic motion because high intensities and long durations of an earthquake motion could lead to significant plastic deformation and prolonged soil liquefaction.Under the strong seismic loading of EQ2,a circular collapse surface,combined with huge settlement and lateral spread,occurred inside the liquefication zone and extended towards the embankment crest.In contrast,in moderate earthquake EQ1,upheaval was observed at each toe of the embankment,and instability occurred only in the liquefied ground.An anti-liquefaction remediation via grouting was determined to significantly reduce liquefaction-induced deformation(settlement,lateral spreading,and local uplift)and restrain the deep-seated circular sliding failure,even though the top sandy soil liquefied in both earthquakes.When the structure was subjected to EQ2 motion,local failure occurred on the embankment slope reinforced with grouting,and thus,an additional appropriate countermeasure should be implemented to further strengthen the slope.For both input motions,the surface deformation of the considered embankment decreased gradually as the thickness of reinforcement was increased,although the reinforcement effect was no longer significant once the thickness exceeded 6 m.展开更多
This study details the low-velocity impact and compression-after-impact(CAI)behaviour of flax fibre-reinforced polymer(FFRP)composites.The impact resistance,energy absorption efficiency and residual compressive streng...This study details the low-velocity impact and compression-after-impact(CAI)behaviour of flax fibre-reinforced polymer(FFRP)composites.The impact resistance,energy absorption efficiency and residual compressive strength as well as the damage pattern of the FFRP composites are compared with the corresponding features of glass fibre-reinforced polymer(GFRP)composites,and the effect of the stacking sequence of FFRP composites is also investigated.The results show that the cross-ply FFRP composites have the highest impact resistance,whereas the multi-directional ply composites have the lowest impact resistance but the highest energy absorption efficiency.The energy absorption efficiency of the FFRP composites is greater than that of the GFRP composites,but the penetration resistance and residual compressive strength of the FFRP composites are lower than those of the GFRP composites with the same stacking sequence,mainly due to the lower tensile strength and elongation at fracture of the FFRP composites.It is also reported that the damage pattern of the FFRP composites is localised cracking and delamination,unlike the overall delamination failure exhibited in the GFRP composites after CAI testing.Finally,the failure mechanisms of the FFRP and GFRP composites are detailed.展开更多
基金funded by the National Natural Science Foundation of China(No.52308316)China Postdoctoral Science Foundation(No.2022M721885)supported by Key Laboratory of Rock Mechanics and Geohazards of Zhejiang Province(No.ZJRMG2022-01)。
文摘The stability of slopes is essential for ensuring safe production in open-pit mines.Analyzing and managing the deformation and failure of the slope rock mass becomes more challenging as the slope height increases.To investigate the damage patterns of slopes with varying heights,three slope models were developed based on a rock slope in Dagushan,China.The deformation failure processes of slopes under the influence of excavation and unloading were analyzed using the base friction test method in combination with digital image technology contrasting.The results supported the following findings:(1)Unloading tensile stress caused lateral partitioning in the slope.Both the foot and top of the slope underwent initial tensile cracks.(2)The destabilization mechanism of unloading deformation in slopes of different heights involved a combination of traction at the foot of the slope or pushing at the top of the slope,followed by accelerated deformation,deceleration creep,and overall destabilization.(3)The unloading damage patterns of slopes at different heights were summarized as follows:compression tension cracking,traction,and slip damage for medium and low slopes;compression tension cracking,traction,and slip failure for the upper part of high slopes;and relaxation tension cracking,pushing,traction,and slip failure for the lower part.Moreover,the upper part of ultra-high slopes exhibited compression tension cracking,traction,and slip failure,while the middle and lower parts displayed relaxation tension cracking,pushing,traction,and slip patterns.Finally,numerical simulations were conducted to verify the results of the test analyses,which demonstrated good consistency.These research results were of great engineering value for proposing effective safety management measures for high slopes.
文摘Through on-site defect investigation,special inspection,and finite element simulation calculation of a high-speed upper-span(30+32+30)m prestressed concrete box girder bridge,the overall sliding force of the bridge on the right side of platform 0#is analyzed.In this situation,typical defects such as overall girder slippage,support dislocation,pier column deviation,and pier bottom side cracks have occurred in the overpass.At the same time,combined with simulation calculation analysis,it is interpreted that the 0#and 1#foundation has been damaged at a certain position below the ground line.The occurrence of broken piles has provided a reliable basis for the later reinforcement and maintenance of the bridge and ideas for emergency inspection and analysis of bridges damaged by the same type of landslides.
文摘BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.
文摘The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.
基金The authors acknowledge support from the Tsinghua University Spring Breeze Fund,Center for Life Sciences,and Institute for Immunology,Tsinghua University,and grants from the Ministry of Science and Technology of China(2021YFC2300500 and 2021YFC2302403)National Natural Science Foundation of China(32141004,81825010,81730043,and 81621002).
文摘All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.
基金The financial support of National Natural Science Foundation of China(Grant Nos.51908288 and 42002266)the project of Key Laboratory of Impact and Safety Engineering(Ningbo University),Ministry of Education is appreciated.
文摘Liquefaction of sandy soils is a big threat to the stability and the safety of an earth embankment laid on saturated soils.A large number of liquefaction-induced damages on embankment due to different types of earthquakes have been reported worldwide.In this research,the dynamic behaviors of earth embankment and the reinforcement effects of grouting as remediation method,subjected to moderate earthquake EQ1 and strong earthquake EQ2,were numerically investigated.The seismic behaviors of ground composed of cohesionless sandy soil and cohesive clayey soil were uniformly described by the cyclic mobility(CM)model,which is capable of describing accurately the mechanical property of the soil due to monotonic and cyclic loadings by accounting for stress-induced anisotropy,over-consolidation,and soil structure.It is known from the numerical investigation that the embankment would experience destructive deformation,and that the collapse mode was closely related to the properties of input seismic motion because high intensities and long durations of an earthquake motion could lead to significant plastic deformation and prolonged soil liquefaction.Under the strong seismic loading of EQ2,a circular collapse surface,combined with huge settlement and lateral spread,occurred inside the liquefication zone and extended towards the embankment crest.In contrast,in moderate earthquake EQ1,upheaval was observed at each toe of the embankment,and instability occurred only in the liquefied ground.An anti-liquefaction remediation via grouting was determined to significantly reduce liquefaction-induced deformation(settlement,lateral spreading,and local uplift)and restrain the deep-seated circular sliding failure,even though the top sandy soil liquefied in both earthquakes.When the structure was subjected to EQ2 motion,local failure occurred on the embankment slope reinforced with grouting,and thus,an additional appropriate countermeasure should be implemented to further strengthen the slope.For both input motions,the surface deformation of the considered embankment decreased gradually as the thickness of reinforcement was increased,although the reinforcement effect was no longer significant once the thickness exceeded 6 m.
基金V.Li acknowledges the financial support from the National Science Fund for Distinguished Young Scholars(Grant No.11625210)National Natural Science Foundation(Grant No.51873153)Fundamental Research Funds for the Central Universities.K.Fu acknowledges the start-up funding from Tongji University.
文摘This study details the low-velocity impact and compression-after-impact(CAI)behaviour of flax fibre-reinforced polymer(FFRP)composites.The impact resistance,energy absorption efficiency and residual compressive strength as well as the damage pattern of the FFRP composites are compared with the corresponding features of glass fibre-reinforced polymer(GFRP)composites,and the effect of the stacking sequence of FFRP composites is also investigated.The results show that the cross-ply FFRP composites have the highest impact resistance,whereas the multi-directional ply composites have the lowest impact resistance but the highest energy absorption efficiency.The energy absorption efficiency of the FFRP composites is greater than that of the GFRP composites,but the penetration resistance and residual compressive strength of the FFRP composites are lower than those of the GFRP composites with the same stacking sequence,mainly due to the lower tensile strength and elongation at fracture of the FFRP composites.It is also reported that the damage pattern of the FFRP composites is localised cracking and delamination,unlike the overall delamination failure exhibited in the GFRP composites after CAI testing.Finally,the failure mechanisms of the FFRP and GFRP composites are detailed.
