Discerning vulnerability differences among different aged trees to drought-driven growth decline or to mortality is critical to implement age-specific countermeasures for forest management in water-limited areas.An im...Discerning vulnerability differences among different aged trees to drought-driven growth decline or to mortality is critical to implement age-specific countermeasures for forest management in water-limited areas.An important species for afforestation in dry environments of northern China,Mongolian pine(Pinus sylvestris var.mongolica Litv.)has recently exhibited growth decline and dieback on many sites,particularly pronounced in old-growth plantations.However,changes in response to drought stress by this species with age as well as the underlying mechanisms are poorly understood.In this study,tree-ring data and remotely sensed vegetation data were combined to investigate variations in growth at individual tree and stand scales for young(9-13 years)and aging(35-52 years)plantations of Mongolian pine in a water-limited area of northern China.A recent decline in tree-ring width in the older plantation also had lower values in satellited-derived normalized difference vegetation indices and normalized difference water indices relative to the younger plantations.In addition,all measured growth-related metrics were strongly correlated with the self-calibrating Palmer drought severity index during the growing season in the older plantation.Sensitivity of growth to drought of the older plantation might be attributed to more severe hydraulic limitations,as reflected by their lower sapwood-and leaf-specific hydraulic conductivities.Our study presents a comprehensive view on changes of growth with age by integrating multiple methods and provides an explanation from the perspective of plant hydraulics for growth decline with age.The results indicate that old-growth Mongolian pine plantations in water-limited environments may face increased growth declines under the context of climate warming and drying.展开更多
Lightweight,flexibility,and low thickness are urgent requirements for next-generation high-performance electromagnetic interference(EMI)shielding materials for catering to the demand for smart and wearable electronic ...Lightweight,flexibility,and low thickness are urgent requirements for next-generation high-performance electromagnetic interference(EMI)shielding materials for catering to the demand for smart and wearable electronic devices.Although several efforts have focused on constructing porous and flexible conductive films or aerogels,few studies have achieved a balance in terms of density,thickness,flexibility,and EMI shielding effectiveness(SE).Herein,an ultrathin,lightweight,and flexible carbon nanotube(CNT)buckypaper enhanced using MXenes(Ti3C2Tx)for high-performance EMI shielding is synthesized through a facile electrophoretic deposition process.The obtained Ti3C2Tx@CNT hybrid buckypaper exhibits an outstanding EMI SE of 60.5 dB in the X-band at 100μm.The hybrid buckypaper with an MXene content of 49.4 wt%exhibits an EMI SE of 50.4 dB in the X-band with a thickness of only 15μm,which is 105%higher than that of pristine CNT buckypaper.Furthermore,an average specific SE value of 5.7×10^(4) dB cm^(2) g^(−1) is exhibited in the 5-μm hybrid buckypaper.Thus,this assembly process proves promising for the construction of ultrathin,flexible,and high-performance EMI shielding films for application in electronic devices and wireless communications.展开更多
Flexible and wearable sensing devices have broad application prospects in bio-monitoring such as pulse measurement,motion detection and voice recognition.In recent years,many significant improvements had been made to ...Flexible and wearable sensing devices have broad application prospects in bio-monitoring such as pulse measurement,motion detection and voice recognition.In recent years,many significant improvements had been made to enhance the sensor’s performance including sensitivity,flexibility and repeatability.However,it is still extremely complicated and difficult to prepare a patterned sensor directly on a flexible substrate.Herein,inspired by typography,a lowcost,environmentally friendly stamping method for the mass production of transparent conductive carbon nanotube(CNT)film is proposed.In this dry transfer strategy,a porous CNT block was used as both the seal and the ink;and Ecoflex film was served as an object substrate.Welldesigned CNT patterns can be easily fabricated on the polymer substrate by engraving the target pattern on the CNT seal before the stamping process.Moreover,the CNT film can be directly used to fabricate ultrathin(300μm)strain sensor.This strain sensor possesses high sensitivity with a gauge factor(GF)up to 9960 at 85%strain,high stretchability(>200%)and repeatability(>5000 cycles).It has been used to measure pulse signals and detect joint motion,suggesting promising application prospects in flexible and wearable electronic devices.展开更多
Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME...Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.展开更多
TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains ...TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRI M22's targeting of the HCV NSSA protein. NS5A is important for HCV replication and for resistance to I FNa therapy. During the first 24 h following the initiation of I FNa treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNα-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNα treatment and Dlavs an important role in controlling HCV replication in vitro.展开更多
Aircraft icing has long been a plague to aviation for its serious threat to flight safety. Even though lots of methods for anti-icing have been in use or studied for quite a long time, new methods are still in great d...Aircraft icing has long been a plague to aviation for its serious threat to flight safety. Even though lots of methods for anti-icing have been in use or studied for quite a long time, new methods are still in great demand for both civil and military aircraft. The current study in this paper uses widely used Dielectric Barrier Discharge(DBD) plasma actuation to anti-ice on a NACA0012 airfoil model with a chord length of 53.5 cm in a closed-circuit icing wind tunnel. An actuator was installed at the leading edge of the airfoil model, and actuated by a pulsed low-temperature plasma power source. The actuator has two types of layout, a striped electrode layout and a meshy electrode layout.The ice accretion process or anti-icing process was recorded by a CCD camera and an infrared camera. Instantaneous pictures and infrared contours show that both types of DBD plasma actuators have the ability for anti-ice under a freestream velocity of 90 m/s, a static temperature of -7℃,an Median Volume droplet Diameter(MVD) of 20 lm, and an Liquid Water Content(LWC) of 0.5 g/m^3. The detected variations of temperatures with time at specific locations reveal that the temperatures oscillate for some time after spraying at first, and then tend to be nearly constant values.This shows that the key point of the anti-icing mechanism with DBD plasma actuation is to achieve a thermal equilibrium on the model surface. Besides, the power consumption in the anti-icing process was estimated in this paper by Lissajous figures measured by an oscilloscope, and it is lower than those of existing anti-icing methods. The experimental results presented in this paper indicate that the DBD plasma anti-icing method is a promising technique in the future.展开更多
Controllable formation of microstructures in the assembled graphene film could tune the physical properties and broaden its applications in flexible electronics.Many efforts have been made to control the formation of ...Controllable formation of microstructures in the assembled graphene film could tune the physical properties and broaden its applications in flexible electronics.Many efforts have been made to control the formation of wrinkles and ripples in graphene films.However,the formation of orderly wrinkles in graphene film remains a challenge.Here,we reported a simple strategy for the fabrication of graphene film with periodic and parallel wrinkles with a pre-stretched polydimethylsiloxane substrate.The width of the wrinkles in graphene can be controlled by changing the pre-stretched strain of the substrate.The average width of wrinkles in graphene film on the substrate with pre-stretched strain of 10%,20%,and 50%was about 3.68,2.99 and 2.01µm,respectively.The morphological evolution of wrinkled double-layered graphene under mechanical deformation was observed and studied.Furthermore,a strain sensor was constructed based on the wrinkled graphene,showing high sensitivity,large working range and excellent cyclic stability.These strain sensors show great potential in real-time motion detection,health surveillance and electronic skins.展开更多
Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk a...Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.展开更多
Seipin plays a vital role in lipid droplet homeostasis,and its deficiency causes congenital generalized lipodystrophy type II in humans.It is not known whether the physiological defects are all caused by cellular lipi...Seipin plays a vital role in lipid droplet homeostasis,and its deficiency causes congenital generalized lipodystrophy type II in humans.It is not known whether the physiological defects are all caused by cellular lipid droplet defects.Loss-of-function mutation of seip-1,the Caenorhabditis elegans seipin ortholog,causes embryonic lethality and lipid droplet abnormality.We uncover nhr-114 and spin-4 as two suppressors of seip-1 embryonic lethality.Mechanistically,nhr-114 and spin-4 act in the“B12-one-carbon cycle-phosphatidylcholine(PC)”axis,and reducing PC synthesis suppresses the embryonic lethality of seip-1 mutants.Conversely,PC deficiency enhances the lipid droplet abnormality of seip-1 mutants.The suppression of seip-1 embryonic lethality by PC reduction requires polyunsaturated fatty acid.In addition,the suppression is enhanced by the knockdown of phospholipid scramblase epg-3.Therefore,seipin and PC exhibit opposite actions in embryogenesis,while they function similarly in lipid droplet homeostasis.Our results demonstrate that seipin-mediated embryogenesis is independent of lipid droplet homeostasis.展开更多
Despite immunotherapy involving immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,the clinical efficacy is limited due to ICI resistance.Pyroptosis is a gasdermin-mediated programmed cell death that...Despite immunotherapy involving immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,the clinical efficacy is limited due to ICI resistance.Pyroptosis is a gasdermin-mediated programmed cell death that enhances responses to ICIs.However,nontargeted elicitation of pyroptosis may induce systemic side effects and toxicity.Therefore,we reasonably design and construct a tumor-specific prodrug that combines the heat shock protein 90 inhibitor tanespimycin(17-AAG)with the photosensitizer chlorin e6(Ce6)to induce pyroptosis,by utilizing the high glutathione level in the tumor microenvironment.The released Ce6 and 17-AAG produce reactive oxygen species by laser triggering,which induces gasdermin E-mediated pyroptosis.Furthermore,17-AAG reduces myeloid-derived suppressor cells and sensitizes tumors to anti-programmed death^(-1)(PD-1)therapy.Thus,our prodrug strategy achieves tumor-targeted pyroptosis to suppress tumor growth,thereby improving the response to anti-PD-1 therapy and extending the survival of 4T1 breast tumor-bearing mice.Consequently,this pyroptosis-based prodrug represents a novel strategy for enforcing immunogenic photodynamic therapy.展开更多
Owing to the conductance-adjustable performance,the emerging two-terminal memristors are promising candidates for artificial synapses and brain-spired neuromorphic computing.Although memristors based on molybdenum dis...Owing to the conductance-adjustable performance,the emerging two-terminal memristors are promising candidates for artificial synapses and brain-spired neuromorphic computing.Although memristors based on molybdenum disulfide(MoS_(2))have displayed outstanding performance,such as thermal stability and high energy efficiency,reports on memristors based on MoS_(2) as the functional layer to simulate synaptic behavior are limited.Herein,a homologous Mo_(2)C/MoS_(2)-based memristor is prepared by partially sulfuring two-dimensional Mo_(2)C crystal.The memristor shows good stability,excellent retention(~104 s)and endurance(>100 cycles),and a high ON/OFF ratio(>10^(3)).Moreover,for comprehensively mimicking biological synapses,the essential synaptic functions of the device are systematically analyzed,including paired-pulse facilitation(PPF),short-term plasticity(STP),long-term plasticity(LTP),long-term depression(LTD),and the transitions from STP to LTP.Notably,this artificial synapse could keep a highlevel stable memory for a long time(60 s)after repeated stimulation.These results prove that our device is highly desirable for biological synapses,which show great potential for application in future high-density storage and neuromorphic computing systems.展开更多
基金financially supported by the National Natural Science Foundation of China(31901093,32220103010,32192431,31722013)National Key R&D Program of China(2020YFA0608100,2022YFF1302505)the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences(ZDBS-LY-DQC019)。
文摘Discerning vulnerability differences among different aged trees to drought-driven growth decline or to mortality is critical to implement age-specific countermeasures for forest management in water-limited areas.An important species for afforestation in dry environments of northern China,Mongolian pine(Pinus sylvestris var.mongolica Litv.)has recently exhibited growth decline and dieback on many sites,particularly pronounced in old-growth plantations.However,changes in response to drought stress by this species with age as well as the underlying mechanisms are poorly understood.In this study,tree-ring data and remotely sensed vegetation data were combined to investigate variations in growth at individual tree and stand scales for young(9-13 years)and aging(35-52 years)plantations of Mongolian pine in a water-limited area of northern China.A recent decline in tree-ring width in the older plantation also had lower values in satellited-derived normalized difference vegetation indices and normalized difference water indices relative to the younger plantations.In addition,all measured growth-related metrics were strongly correlated with the self-calibrating Palmer drought severity index during the growing season in the older plantation.Sensitivity of growth to drought of the older plantation might be attributed to more severe hydraulic limitations,as reflected by their lower sapwood-and leaf-specific hydraulic conductivities.Our study presents a comprehensive view on changes of growth with age by integrating multiple methods and provides an explanation from the perspective of plant hydraulics for growth decline with age.The results indicate that old-growth Mongolian pine plantations in water-limited environments may face increased growth declines under the context of climate warming and drying.
基金National Natural Science Foundation of China(Grant Nos.52072415,52072306 and 51772335)the Science and Technology Program of Guangzhou(201904010450)Science Foundation of the National Key Laboratory of Science and Technology on Advanced Composites in Special Environments(6142905192509).
文摘Lightweight,flexibility,and low thickness are urgent requirements for next-generation high-performance electromagnetic interference(EMI)shielding materials for catering to the demand for smart and wearable electronic devices.Although several efforts have focused on constructing porous and flexible conductive films or aerogels,few studies have achieved a balance in terms of density,thickness,flexibility,and EMI shielding effectiveness(SE).Herein,an ultrathin,lightweight,and flexible carbon nanotube(CNT)buckypaper enhanced using MXenes(Ti3C2Tx)for high-performance EMI shielding is synthesized through a facile electrophoretic deposition process.The obtained Ti3C2Tx@CNT hybrid buckypaper exhibits an outstanding EMI SE of 60.5 dB in the X-band at 100μm.The hybrid buckypaper with an MXene content of 49.4 wt%exhibits an EMI SE of 50.4 dB in the X-band with a thickness of only 15μm,which is 105%higher than that of pristine CNT buckypaper.Furthermore,an average specific SE value of 5.7×10^(4) dB cm^(2) g^(−1) is exhibited in the 5-μm hybrid buckypaper.Thus,this assembly process proves promising for the construction of ultrathin,flexible,and high-performance EMI shielding films for application in electronic devices and wireless communications.
基金financially supported by National Natural Science Foundation of China(Grant No.51772335)Guangdong Youth Top-notch Talent Support Program(No.2015TQ01C201)the Fundamental Research Funds for the Central Universities.
文摘Flexible and wearable sensing devices have broad application prospects in bio-monitoring such as pulse measurement,motion detection and voice recognition.In recent years,many significant improvements had been made to enhance the sensor’s performance including sensitivity,flexibility and repeatability.However,it is still extremely complicated and difficult to prepare a patterned sensor directly on a flexible substrate.Herein,inspired by typography,a lowcost,environmentally friendly stamping method for the mass production of transparent conductive carbon nanotube(CNT)film is proposed.In this dry transfer strategy,a porous CNT block was used as both the seal and the ink;and Ecoflex film was served as an object substrate.Welldesigned CNT patterns can be easily fabricated on the polymer substrate by engraving the target pattern on the CNT seal before the stamping process.Moreover,the CNT film can be directly used to fabricate ultrathin(300μm)strain sensor.This strain sensor possesses high sensitivity with a gauge factor(GF)up to 9960 at 85%strain,high stretchability(>200%)and repeatability(>5000 cycles).It has been used to measure pulse signals and detect joint motion,suggesting promising application prospects in flexible and wearable electronic devices.
基金supported by grants from the China Postdoctoral Science Foundation(Grant No.2022M712880)the Program of the Major Research Plan of the National Natural Science Foundation of China(Grant No.91942314)the National Natural Science Foundation of China(Grant No.82001659).
文摘Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.
文摘TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRI M22's targeting of the HCV NSSA protein. NS5A is important for HCV replication and for resistance to I FNa therapy. During the first 24 h following the initiation of I FNa treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNα-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNα treatment and Dlavs an important role in controlling HCV replication in vitro.
基金supported by the National Natural Science Foundation of China (No.11472221)
文摘Aircraft icing has long been a plague to aviation for its serious threat to flight safety. Even though lots of methods for anti-icing have been in use or studied for quite a long time, new methods are still in great demand for both civil and military aircraft. The current study in this paper uses widely used Dielectric Barrier Discharge(DBD) plasma actuation to anti-ice on a NACA0012 airfoil model with a chord length of 53.5 cm in a closed-circuit icing wind tunnel. An actuator was installed at the leading edge of the airfoil model, and actuated by a pulsed low-temperature plasma power source. The actuator has two types of layout, a striped electrode layout and a meshy electrode layout.The ice accretion process or anti-icing process was recorded by a CCD camera and an infrared camera. Instantaneous pictures and infrared contours show that both types of DBD plasma actuators have the ability for anti-ice under a freestream velocity of 90 m/s, a static temperature of -7℃,an Median Volume droplet Diameter(MVD) of 20 lm, and an Liquid Water Content(LWC) of 0.5 g/m^3. The detected variations of temperatures with time at specific locations reveal that the temperatures oscillate for some time after spraying at first, and then tend to be nearly constant values.This shows that the key point of the anti-icing mechanism with DBD plasma actuation is to achieve a thermal equilibrium on the model surface. Besides, the power consumption in the anti-icing process was estimated in this paper by Lissajous figures measured by an oscilloscope, and it is lower than those of existing anti-icing methods. The experimental results presented in this paper indicate that the DBD plasma anti-icing method is a promising technique in the future.
基金This work was financially supported by the National Natural Science Foundation of China(51772335)the Science and Technology Program of Guangzhou(201904010450).
文摘Controllable formation of microstructures in the assembled graphene film could tune the physical properties and broaden its applications in flexible electronics.Many efforts have been made to control the formation of wrinkles and ripples in graphene films.However,the formation of orderly wrinkles in graphene film remains a challenge.Here,we reported a simple strategy for the fabrication of graphene film with periodic and parallel wrinkles with a pre-stretched polydimethylsiloxane substrate.The width of the wrinkles in graphene can be controlled by changing the pre-stretched strain of the substrate.The average width of wrinkles in graphene film on the substrate with pre-stretched strain of 10%,20%,and 50%was about 3.68,2.99 and 2.01µm,respectively.The morphological evolution of wrinkled double-layered graphene under mechanical deformation was observed and studied.Furthermore,a strain sensor was constructed based on the wrinkled graphene,showing high sensitivity,large working range and excellent cyclic stability.These strain sensors show great potential in real-time motion detection,health surveillance and electronic skins.
基金financially supported by National Natural Science Foundation of China(82072996,81874131,51703187)the National Key Research and Development Program(2017YFSF090107,China)+3 种基金the Hubei Province Natural Science Funds for Distinguished Young Scholar(2017CFA062,China)Innovative research team of high-level local universities in Shanghai(ZLCX20180500,China)Chongqing Talents of Exceptional Young Talents Project(CQYC202005029 and cstc2021ycjh-bgzxm0061,China)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2021017)。
文摘Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.
基金supported by the National Natural Science Foundation of China(9195420001)the Ministry of Science and Technology of China(2018YFA0506902).
文摘Seipin plays a vital role in lipid droplet homeostasis,and its deficiency causes congenital generalized lipodystrophy type II in humans.It is not known whether the physiological defects are all caused by cellular lipid droplet defects.Loss-of-function mutation of seip-1,the Caenorhabditis elegans seipin ortholog,causes embryonic lethality and lipid droplet abnormality.We uncover nhr-114 and spin-4 as two suppressors of seip-1 embryonic lethality.Mechanistically,nhr-114 and spin-4 act in the“B12-one-carbon cycle-phosphatidylcholine(PC)”axis,and reducing PC synthesis suppresses the embryonic lethality of seip-1 mutants.Conversely,PC deficiency enhances the lipid droplet abnormality of seip-1 mutants.The suppression of seip-1 embryonic lethality by PC reduction requires polyunsaturated fatty acid.In addition,the suppression is enhanced by the knockdown of phospholipid scramblase epg-3.Therefore,seipin and PC exhibit opposite actions in embryogenesis,while they function similarly in lipid droplet homeostasis.Our results demonstrate that seipin-mediated embryogenesis is independent of lipid droplet homeostasis.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.82072996(Z.-J.S.),81874131(Z.-J.S.),and 51703187(Z.X.))National Key Research and Development Program(No.2017YFSF090107)+2 种基金the Chongqing Talent Plan for Young TopNotch Talents(No.CQYC202005029(Z.X.))the Hubei Province Natural Science Funds for Distinguished Young Scholar(No.2017CFA062(Z.-J.S.))Innovative Research Team of High-level Local Universities in Shanghai(No.ZLCX20180500(Z.-J.S.)).
文摘Despite immunotherapy involving immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,the clinical efficacy is limited due to ICI resistance.Pyroptosis is a gasdermin-mediated programmed cell death that enhances responses to ICIs.However,nontargeted elicitation of pyroptosis may induce systemic side effects and toxicity.Therefore,we reasonably design and construct a tumor-specific prodrug that combines the heat shock protein 90 inhibitor tanespimycin(17-AAG)with the photosensitizer chlorin e6(Ce6)to induce pyroptosis,by utilizing the high glutathione level in the tumor microenvironment.The released Ce6 and 17-AAG produce reactive oxygen species by laser triggering,which induces gasdermin E-mediated pyroptosis.Furthermore,17-AAG reduces myeloid-derived suppressor cells and sensitizes tumors to anti-programmed death^(-1)(PD-1)therapy.Thus,our prodrug strategy achieves tumor-targeted pyroptosis to suppress tumor growth,thereby improving the response to anti-PD-1 therapy and extending the survival of 4T1 breast tumor-bearing mice.Consequently,this pyroptosis-based prodrug represents a novel strategy for enforcing immunogenic photodynamic therapy.
基金financially supported by the National Natural Science Foundation of China (grant no.52072415)Guangdong Basic and Applied Basic Research Foundation (grant nos.2021A1515012387,and 2021A1515110980)。
文摘Owing to the conductance-adjustable performance,the emerging two-terminal memristors are promising candidates for artificial synapses and brain-spired neuromorphic computing.Although memristors based on molybdenum disulfide(MoS_(2))have displayed outstanding performance,such as thermal stability and high energy efficiency,reports on memristors based on MoS_(2) as the functional layer to simulate synaptic behavior are limited.Herein,a homologous Mo_(2)C/MoS_(2)-based memristor is prepared by partially sulfuring two-dimensional Mo_(2)C crystal.The memristor shows good stability,excellent retention(~104 s)and endurance(>100 cycles),and a high ON/OFF ratio(>10^(3)).Moreover,for comprehensively mimicking biological synapses,the essential synaptic functions of the device are systematically analyzed,including paired-pulse facilitation(PPF),short-term plasticity(STP),long-term plasticity(LTP),long-term depression(LTD),and the transitions from STP to LTP.Notably,this artificial synapse could keep a highlevel stable memory for a long time(60 s)after repeated stimulation.These results prove that our device is highly desirable for biological synapses,which show great potential for application in future high-density storage and neuromorphic computing systems.