Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self...Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.展开更多
This paper develops a semi-analytical solution for pile penetration in natural soft clays using the strain path method(SPM).The stress-strain behavior of soils is characterized by the S-CLAY1S model,which can capture ...This paper develops a semi-analytical solution for pile penetration in natural soft clays using the strain path method(SPM).The stress-strain behavior of soils is characterized by the S-CLAY1S model,which can capture the anisotropic evolution and destructuring nature of soft clays.By integrating the S-CLAY1S model into the theoretical framework of the SPM,a set of ordinary differential equations is formulated with respect to the vertical coordinate of soil particles.The distribution of excess pore water pressure(EPWP)following pile installation is approximated through one-dimensional(1D)radial integration around the pile shaft.The distribution of stresses and EPWP,along with the evolution of fabric anisotropy within the soil surrounding the pile,is presented to illustrate the response of pile penetration in natural soft clays.The proposed solution is validated against existing theoretical solutions using the SPM and cavity expansion method(CEM),along with experimental data.The findings demonstrate that the SPM reveals lower radial effective stresses and EPWP at the pile shaft than that of CEM.Pile penetration alters the soil's anisotropic properties,inducing rotational hardening and affecting post-installation stress distribution.Soil destructuration eliminates bonding among particles near the pile,resulting in a complete disruption of soil structure at the pile surface,which is particularly pronounced for higher initial soil structure ratios.Minimal variation was observed in the three principal stresses and shear stress on the cone side surface as the angle increased from 18°to 60°,except for a slight reduction in EPWP.展开更多
The effects of seemingly inert alkali metal(AM)cations on the electrocatalytic activity of electrode materials towards reactions essential for energy provision have become the emphasis of substantial research efforts ...The effects of seemingly inert alkali metal(AM)cations on the electrocatalytic activity of electrode materials towards reactions essential for energy provision have become the emphasis of substantial research efforts in recent years.The hydrogen and oxygen evolution reactions during alkaline water electrolysis and the oxygen electro-reduction taking place in fuel cells are of particular importance.There is no universal theory explaining all the details of the AM cation effect in electrocatalysis.For example,it remains unclear how“spectator”AM-cations can change the kinetics of electrocatalytic reactions often more significantly than the modifications of the elec-trode structure and composition.This situation originates partly from a lack of systematic experimental and theoretical studies of this phenomenon.The present work exploits impedance spectroscopy to investigate the influence of the AM cations on the mechanism of the hydrogen evolution reaction at Pt microelectrodes.The activity follows the trend:Li^(+)≥Na^(+)≥K^(+)≥Cs^(+),where the highest activity corresponds to 0.1 M LiOH electrolytes at low overpotentials.We demonstrate that the nature of the AM cations also changes the relative contribution of the Volmer–Heyrovsky and Volmer–Tafel mechanisms to the overall reaction,with the former being more important for LiOH electrolytes.Our density functional theory-based thermodynamics and molecular dynamics calculations support these findings.展开更多
The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and main...The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.展开更多
To further expand the application of Mg alloys at high temperatures,the oxidation resistance of Mg-0.3Ca and Mg-3.6Ca alloys with protective coating under flame exposure was studied.Results show that the oxidation res...To further expand the application of Mg alloys at high temperatures,the oxidation resistance of Mg-0.3Ca and Mg-3.6Ca alloys with protective coating under flame exposure was studied.Results show that the oxidation resistance of Mg-Ca alloys under flame exposure is significantly improved by the protective coating,and Mg-3.6Ca alloy shows better oxidation resistance performance.The surface temperature of Mg-Ca alloys is reduced by the coating,therefore improving the oxidation resistance under flame exposure.However,the thermal insulation effect of the coating on Mg-3.6Ca alloy is better,which can be attributed to the Ca accumulation on the surface film.In addition,the surface film with Ca accumulation layer plays a crucial role in protecting the alloy.No obvious Ca accumulation layer exists on the Mg-0.3Ca alloy surface,presenting a restricted protective effect.Nevertheless,the surface film containing Ca accumulation layer is formed on Mg-3.6 Ca alloy,which shows an excellent protective effect.展开更多
BACKGROUND Pancreatic cystic lesions are common in patients eligible for solid organ transplan-tation.It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancie...BACKGROUND Pancreatic cystic lesions are common in patients eligible for solid organ transplan-tation.It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancies in organ recipients.However,the impact of immunosuppression on pancreatic cystic lesions is yet unknown.AIM To evaluate the prevalence of pancreatic cystic lesions and the risk of cyst progression in immunosuppressed patients.METHODS A systematic literature search was performed in relevant databases.Studies reporting either on the prevalence and/or the incidence of pancreatic cyst progression compared to a control group were implemented in the first systematic review and meta-analysis on this topic.RESULTS The prevalence of pancreatic cystic lesions was comparable with 7%(95%CI:5%-11%)in the immunosuppressed cohort and 9%(95%CI:5%-16%)in the control cohort.The mean cyst size increase in the immunosuppression group was 3.2 mm(range 1.0-5.2mm)compared to 3.5 mm(1.0-6.9)in the control group(standar-dized mean difference 0.0 mm,95%CI:-0.3-0.2 mm,P=0.72).There was also no significant increase in the development of resection criteria or worrisome features under immunosuppression either[relative risk 1.1(fixed effect model),1.2(ran-dom effects model),P=0.61].CONCLUSION Immunosuppression does not increase the prevalence of pancreatic cystic lesions,nor does it increase the risk of cyst progression in terms of cyst size and development of resection criteria.Therefore,pancreatic cystic lesions in transplant candidates should not be a contraindication for solid organ transplantation.展开更多
Subretinal injection is a complicated task for retinal surgeons to operate manually.In this paper we demonstrate a robust framework for needle detection and localisation in robotassisted subretinal injection using mic...Subretinal injection is a complicated task for retinal surgeons to operate manually.In this paper we demonstrate a robust framework for needle detection and localisation in robotassisted subretinal injection using microscope-integrated Optical Coherence Tomography with deep learning.Five convolutional neural networks with different architectures were evaluated.The main differences between the architectures are the amount of information they receive at the input layer.When evaluated on ex-vivo pig eyes,the top performing network successfully detected all needles in the dataset and localised them with an Intersection over Union value of 0.55.The algorithm was evaluated by comparing the depth of the top and bottom edge of the predicted bounding box to the ground truth.This analysis showed that the top edge can be used to predict the depth of the needle with a maximum error of 8.5μm.展开更多
The integration of artificial intelligence(AI)into medical robotics has emerged as a cornerstone of modern healthcare,driving transformative advancements in precision,adaptability and patient outcomes.Although computa...The integration of artificial intelligence(AI)into medical robotics has emerged as a cornerstone of modern healthcare,driving transformative advancements in precision,adaptability and patient outcomes.Although computational tools have long supported diagnostic processes,their role is evolving beyond passive assistance to become active collaborators in therapeutic decision-making.In this paradigm,knowledge-driven deep learning systems are redefining possibilities-enabling robots to interpret complex data,adapt to dynamic clinical environments and execute tasks with human-like contextual awareness.展开更多
To address challenges related to the intermittency of renewable energy sources,aqueous potassium-ion batteries(AKIBs)are a promising and sustainable alternative to conventional systems for large-scale energy storage.T...To address challenges related to the intermittency of renewable energy sources,aqueous potassium-ion batteries(AKIBs)are a promising and sustainable alternative to conventional systems for large-scale energy storage.To enable their practical application,maximizing energy density and longevity while minimizing production and material costs is a key goal.In this work,we propose an AKIB consisting only of abundant and cost-efficient materials,which delivers a high energy density of more than 70 Wh kg^(-1).We combine simple strategies to stabilize the Mn-rich Prussian blue analog cathode by Fe-doping,improving the crystallinity,and tuning the electrolyte composition without employing expensive water-in-salt electrolytes.Using a mixed 2.5 M Ca(NO_(3))_(2)+1.5 M KNO_(3)electrolyte,we assemble a novel AKIB with a Fe-doped manganese hexacyanoferrate cathode and an organic poly(naphthalene-4-formylethylenediamine)anode.Besides a high energy density,the full cell delivers a specific capacity of approximately 60 mAhg^(-1),a power density of 5000 W kg^(-1),and 80% capacity retention after 600 cycles.展开更多
We analyze the absorption features in the public 73 ks XMM-Newton spectra of the Seyfert 1 galaxy PG 0052+251.Our analysis reveals the presence of a warm absorber(WA)intrinsic to the source and the hot circumgalactic ...We analyze the absorption features in the public 73 ks XMM-Newton spectra of the Seyfert 1 galaxy PG 0052+251.Our analysis reveals the presence of a warm absorber(WA)intrinsic to the source and the hot circumgalactic medium at zero redshift.The identified WA is inflowing toward the central black hole,with a velocity shift of■.The ionization parameter of the WA is■,showing strong O II and O III absorption lines,along with a significant absorption of the spectral continuum at?10?.The line of sight toward PG 0052+251 intersects the halo of M31 at an impact parameter of approximately 218 kpc.Several local(z~0)absorption lines,like O VII,O VIII,and Ne IX,were detected.The derived hydrogen column density of the local hot gas is 2.2–2.6σhigher than those estimated by several models of the Galactic hot halo,suggesting a likely contribution from the M31 halo.We also find two absorption features at24.305?and 21.410?,which are unlikely to be associated with the hot halos or the warm-hot intergalactic medium but imply the presence of an additional WA component with an outflow velocity of approximately-7000 km s^(-1).展开更多
基金supported by the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University(No.2024LZXNYDJ017)the Project Program of the Science and Technology Department of Sichuan Province(No.2025zNSFSC0679)the Project Program of Chongqing Science and Technology Bureau(No.cstc2020jcyjmsxmX1037).
文摘Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.
基金support from the National Natural Science Foundation of China(Grant No.42407256)the State Key Laboratory of Hydraulics and Mountain River Engineering,China(Grant No.SKHL2113)the Sichuan Science and Technology Program(Grant No.2024YFHZ0341).
文摘This paper develops a semi-analytical solution for pile penetration in natural soft clays using the strain path method(SPM).The stress-strain behavior of soils is characterized by the S-CLAY1S model,which can capture the anisotropic evolution and destructuring nature of soft clays.By integrating the S-CLAY1S model into the theoretical framework of the SPM,a set of ordinary differential equations is formulated with respect to the vertical coordinate of soil particles.The distribution of excess pore water pressure(EPWP)following pile installation is approximated through one-dimensional(1D)radial integration around the pile shaft.The distribution of stresses and EPWP,along with the evolution of fabric anisotropy within the soil surrounding the pile,is presented to illustrate the response of pile penetration in natural soft clays.The proposed solution is validated against existing theoretical solutions using the SPM and cavity expansion method(CEM),along with experimental data.The findings demonstrate that the SPM reveals lower radial effective stresses and EPWP at the pile shaft than that of CEM.Pile penetration alters the soil's anisotropic properties,inducing rotational hardening and affecting post-installation stress distribution.Soil destructuration eliminates bonding among particles near the pile,resulting in a complete disruption of soil structure at the pile surface,which is particularly pronounced for higher initial soil structure ratios.Minimal variation was observed in the three principal stresses and shear stress on the cone side surface as the angle increased from 18°to 60°,except for a slight reduction in EPWP.
基金the German Research Foundation (DFG) under Germany's excellence strategy–EXC 2089/1–390776260, Germany's excellence cluster “e-conversion”the DFG project BA 5795/6-1+2 种基金funding from the European Union's Horizon 2020 research and innovation program under grant agreement HERMES No 952184the National Science Foundation (NSF) support through the NSF CAREER award (Grant No. CBET1941204)financial support from TUM Innovation Network for Artificial Intelligence powered Multifunctional Material Design (ARTEMIS).
文摘The effects of seemingly inert alkali metal(AM)cations on the electrocatalytic activity of electrode materials towards reactions essential for energy provision have become the emphasis of substantial research efforts in recent years.The hydrogen and oxygen evolution reactions during alkaline water electrolysis and the oxygen electro-reduction taking place in fuel cells are of particular importance.There is no universal theory explaining all the details of the AM cation effect in electrocatalysis.For example,it remains unclear how“spectator”AM-cations can change the kinetics of electrocatalytic reactions often more significantly than the modifications of the elec-trode structure and composition.This situation originates partly from a lack of systematic experimental and theoretical studies of this phenomenon.The present work exploits impedance spectroscopy to investigate the influence of the AM cations on the mechanism of the hydrogen evolution reaction at Pt microelectrodes.The activity follows the trend:Li^(+)≥Na^(+)≥K^(+)≥Cs^(+),where the highest activity corresponds to 0.1 M LiOH electrolytes at low overpotentials.We demonstrate that the nature of the AM cations also changes the relative contribution of the Volmer–Heyrovsky and Volmer–Tafel mechanisms to the overall reaction,with the former being more important for LiOH electrolytes.Our density functional theory-based thermodynamics and molecular dynamics calculations support these findings.
基金supported by the German Research Foundation(Deutsche Forschungsgemeinschaft)(DFG),project number 422179811 to RR and RA 689/12-1 to GR.
文摘The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.
基金General Project of Natural Science Research in Higher Education Institutions in Jiangsu Province(23KJB430039)Major Natural Science Research Project of Higher Education Institutions in Jiangsu Province(21KJA460007)National Natural Science Foundation of China(51905462)。
文摘To further expand the application of Mg alloys at high temperatures,the oxidation resistance of Mg-0.3Ca and Mg-3.6Ca alloys with protective coating under flame exposure was studied.Results show that the oxidation resistance of Mg-Ca alloys under flame exposure is significantly improved by the protective coating,and Mg-3.6Ca alloy shows better oxidation resistance performance.The surface temperature of Mg-Ca alloys is reduced by the coating,therefore improving the oxidation resistance under flame exposure.However,the thermal insulation effect of the coating on Mg-3.6Ca alloy is better,which can be attributed to the Ca accumulation on the surface film.In addition,the surface film with Ca accumulation layer plays a crucial role in protecting the alloy.No obvious Ca accumulation layer exists on the Mg-0.3Ca alloy surface,presenting a restricted protective effect.Nevertheless,the surface film containing Ca accumulation layer is formed on Mg-3.6 Ca alloy,which shows an excellent protective effect.
文摘BACKGROUND Pancreatic cystic lesions are common in patients eligible for solid organ transplan-tation.It has been shown that the need for immunosuppression after organ transplantation increases the rate of malignancies in organ recipients.However,the impact of immunosuppression on pancreatic cystic lesions is yet unknown.AIM To evaluate the prevalence of pancreatic cystic lesions and the risk of cyst progression in immunosuppressed patients.METHODS A systematic literature search was performed in relevant databases.Studies reporting either on the prevalence and/or the incidence of pancreatic cyst progression compared to a control group were implemented in the first systematic review and meta-analysis on this topic.RESULTS The prevalence of pancreatic cystic lesions was comparable with 7%(95%CI:5%-11%)in the immunosuppressed cohort and 9%(95%CI:5%-16%)in the control cohort.The mean cyst size increase in the immunosuppression group was 3.2 mm(range 1.0-5.2mm)compared to 3.5 mm(1.0-6.9)in the control group(standar-dized mean difference 0.0 mm,95%CI:-0.3-0.2 mm,P=0.72).There was also no significant increase in the development of resection criteria or worrisome features under immunosuppression either[relative risk 1.1(fixed effect model),1.2(ran-dom effects model),P=0.61].CONCLUSION Immunosuppression does not increase the prevalence of pancreatic cystic lesions,nor does it increase the risk of cyst progression in terms of cyst size and development of resection criteria.Therefore,pancreatic cystic lesions in transplant candidates should not be a contraindication for solid organ transplantation.
基金ZJU 100 Young Talent ProgramKey Program for Robot-assisted Subretinal Injection Research Center in Zhejiang Province,Grant/Award Number:2023ZY1061。
文摘Subretinal injection is a complicated task for retinal surgeons to operate manually.In this paper we demonstrate a robust framework for needle detection and localisation in robotassisted subretinal injection using microscope-integrated Optical Coherence Tomography with deep learning.Five convolutional neural networks with different architectures were evaluated.The main differences between the architectures are the amount of information they receive at the input layer.When evaluated on ex-vivo pig eyes,the top performing network successfully detected all needles in the dataset and localised them with an Intersection over Union value of 0.55.The algorithm was evaluated by comparing the depth of the top and bottom edge of the predicted bounding box to the ground truth.This analysis showed that the top edge can be used to predict the depth of the needle with a maximum error of 8.5μm.
文摘The integration of artificial intelligence(AI)into medical robotics has emerged as a cornerstone of modern healthcare,driving transformative advancements in precision,adaptability and patient outcomes.Although computational tools have long supported diagnostic processes,their role is evolving beyond passive assistance to become active collaborators in therapeutic decision-making.In this paradigm,knowledge-driven deep learning systems are redefining possibilities-enabling robots to interpret complex data,adapt to dynamic clinical environments and execute tasks with human-like contextual awareness.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under Germany’s Excellence Strategy-EXC 2089/1-390776260(e-conversion)for fundingfinancial support from TUM Innovation Network for Artificial Intelligence powered Multifunctional Material Design(ARTEMIS)。
文摘To address challenges related to the intermittency of renewable energy sources,aqueous potassium-ion batteries(AKIBs)are a promising and sustainable alternative to conventional systems for large-scale energy storage.To enable their practical application,maximizing energy density and longevity while minimizing production and material costs is a key goal.In this work,we propose an AKIB consisting only of abundant and cost-efficient materials,which delivers a high energy density of more than 70 Wh kg^(-1).We combine simple strategies to stabilize the Mn-rich Prussian blue analog cathode by Fe-doping,improving the crystallinity,and tuning the electrolyte composition without employing expensive water-in-salt electrolytes.Using a mixed 2.5 M Ca(NO_(3))_(2)+1.5 M KNO_(3)electrolyte,we assemble a novel AKIB with a Fe-doped manganese hexacyanoferrate cathode and an organic poly(naphthalene-4-formylethylenediamine)anode.Besides a high energy density,the full cell delivers a specific capacity of approximately 60 mAhg^(-1),a power density of 5000 W kg^(-1),and 80% capacity retention after 600 cycles.
基金supported by the National Natural Science Foundation of China under Nos.11890692,12133008 and 12221003We acknowledge the science research grant from the China Manned Space Project with No.CMS-CSST-2021-A04.
文摘We analyze the absorption features in the public 73 ks XMM-Newton spectra of the Seyfert 1 galaxy PG 0052+251.Our analysis reveals the presence of a warm absorber(WA)intrinsic to the source and the hot circumgalactic medium at zero redshift.The identified WA is inflowing toward the central black hole,with a velocity shift of■.The ionization parameter of the WA is■,showing strong O II and O III absorption lines,along with a significant absorption of the spectral continuum at?10?.The line of sight toward PG 0052+251 intersects the halo of M31 at an impact parameter of approximately 218 kpc.Several local(z~0)absorption lines,like O VII,O VIII,and Ne IX,were detected.The derived hydrogen column density of the local hot gas is 2.2–2.6σhigher than those estimated by several models of the Galactic hot halo,suggesting a likely contribution from the M31 halo.We also find two absorption features at24.305?and 21.410?,which are unlikely to be associated with the hot halos or the warm-hot intergalactic medium but imply the presence of an additional WA component with an outflow velocity of approximately-7000 km s^(-1).
