Clostridioides difficile(C.difficile)is one of the major causes of nosocomial infections.Pregnant women,who are generally considered at low risk for C.difficile infection(CDI),have attracted attention because of an in...Clostridioides difficile(C.difficile)is one of the major causes of nosocomial infections.Pregnant women,who are generally considered at low risk for C.difficile infection(CDI),have attracted attention because of an increasing number of reports.Oral vancomycin,the only first-line treatment for pregnant women infected with C.difficile,has been associated with increasing strain resistance,leading to decreased efficacy.Fecal microbiota transplantation(FMT)is recommended for severe,fulminant,and recurrent CDI;however,it is generally avoided in pregnant women because of safety concerns.We report a case of a pregnant woman with a primary ribotype 027 CDI who experienced a successful outcome with washed microbiota transplantation(WMT),an improved form of FMT,via enema.The specific strain of ribotype 027 is related to severe outcomes but has not previously been reported in pregnant women.The follow-up lasted for two years,during which the patient's diarrhea was fully alleviated without recurrence.The baby showed normal growth and development,and no adverse events were recorded for either.This case provides evidence for the efficacy and safety of WMT in pregnant women infected with C.difficile,indicating that WMT via enema may be a viable therapeutic strategy for this population for treating CDI.展开更多
The variable flexibility of a fish body is believed to play a significant role in improving swimming performance.To explore the effect of non-uniform flexibility on the motion performance of fish under biologically re...The variable flexibility of a fish body is believed to play a significant role in improving swimming performance.To explore the effect of non-uniform flexibility on the motion performance of fish under biologically relevant conditions,we set up three different flexible distribution modes for a semi-free filament and compared the motion performance of different flexible distribution modes through numerical simulations.The filament is located in the wake of the front flapping foil;it can swing adaptively in the lateral direction according to the flow situation of the surrounding fluid and finally reach a stable position.The results show that the motion state of the filament will alter with a change in the flexibility of the filament,from moving in the vortex street to moving on the side of the vortex street.In the Bénard-von Kármán(BvK)vortex streets,the drag coefficient of the filament increases as the flexibility of the filament increases,and the value of the drag coefficient is at a minimum when the flexibility of the filament increases linearly along the length of the filament.Further investigation indicates that at 85%–90%of the filament length(starting from the leading edge),the flexibility of the filament begins to increase significantly,and the filament can obtain its best propulsion performance.The results of this work provide new insights into the role of non-uniform flexibility during the process of fish movement and provide a valuable reference for the design of bionic underwater vehicles.展开更多
The hydrodynamics in fish school are studied through simulating the flow over two wiggling hydrofoils in diagonal arrangement by using the immersed boundary method, both in-phase and anti-phase wiggling motions are co...The hydrodynamics in fish school are studied through simulating the flow over two wiggling hydrofoils in diagonal arrangement by using the immersed boundary method, both in-phase and anti-phase wiggling motions are considered in this study, the effect of the longitudinal spacing on the hydrodynamic performance has been investigated. It is revealed that, when the longitudinal spacing is smaller than body length, the diagonal formation is helpful to the follower but harmful to the leader;when the longitudinal spacing is larger than body length, the opposite effect is occurring;and a significant enhancement of the propulsive performance is obtained when the longitudinal spacing is optimized.展开更多
At low Reynolds numbers,the variable flexibility of flapping insect wings is considered essential in improving the favorable aerodynamic forces.To further explore whether significant aerodynamic coupling exists betwee...At low Reynolds numbers,the variable flexibility of flapping insect wings is considered essential in improving the favorable aerodynamic forces.To further explore whether significant aerodynamic coupling exists between the microstructure and passive flexible deformation,this paper proposes three technical comparison airfoils:a corrugated wing with deformation,a symmetric flat plate wing with deformation,and a corrugated wing without deformation.Based on STAR-CCM+software,this paper numerically solves the Navier-Stokes equations using the fluid-structure interaction method.The results show that the aerodynamic performance of the flexible corrugated wing is better than that of the rigid corrugated wing,and its lift and thrust are both improved to a certain extent,and the thrust efficiency of the flexible corrugated wing is significantly higher than that of the flexible flat plate.Although the thrust is improved,a part of the lift is lost,and as the flapping amplitude increases past 35°,the disparity gradually increases.A comparison of the flexible technical airfoils shows that the corrugated structure promotes thrust and retards lift,which is closely related to the formation and dissipation of strong vortex rings during the downstroke phase.On the premise of maintaining typical flapping without falling,dragonflies can fly with skillful efficiency by adjusting the way they flap their wings.The results of this work provide new insight into the formation and role of thrust in flapping maneuvering flight and provide a specific reference for developing new bionic flapping-wing aircraft.展开更多
The quantification of hydrogen peroxide(H_(2)O_(2))generated in the plasma-liquid interactions is of great importance,since the H_(2)O_(2)species is vital for the applications of the plasma-liquid system.Herein,we rep...The quantification of hydrogen peroxide(H_(2)O_(2))generated in the plasma-liquid interactions is of great importance,since the H_(2)O_(2)species is vital for the applications of the plasma-liquid system.Herein,we report on in situ quantification of the aqueous H_(2)O_(2)(H_(2)O_(2)aq)using a colorimetric method for the DC plasma-liquid systems with liquid as either a cathode or an anode.The results show that the H_(2)O_(2)aqyield is 8-12 times larger when the liquid acts as a cathode than when the liquid acts as an anode.The conversion rate of the gaseous OH radicals to H_(2)O_(2)aqis 4-6 times greater in the former case.However,the concentrations of dissolved OH radicals for both liquid as cathode and anode are of the same order of tens of n M.展开更多
The vortex formation and organization are the key to understand the intrinsic mechanism in flying and swimming in nature. The vortex wake of dual-flapping foils is numerically investigated using the immersed boundary ...The vortex formation and organization are the key to understand the intrinsic mechanism in flying and swimming in nature. The vortex wake of dual-flapping foils is numerically investigated using the immersed boundary method. Beside the deflection of the reversed von-Kármán vortex street, an interesting phenomenon, the deflection of the von-Kármán vortex street, is observed behind the dual-flapping foils. The deflected direction is not according to the initial direction of biplane’s flapping motion. And the deflection angle is related to the difference between upward and downward deflecting velocities.展开更多
The propulsive performance of an oblique school of fish is numerically studied using an immersed boundary technique. The effect of the spacing and wiggling phase on the hydrodynamics of the system is investigated. The...The propulsive performance of an oblique school of fish is numerically studied using an immersed boundary technique. The effect of the spacing and wiggling phase on the hydrodynamics of the system is investigated. The hydrodynamics of the system is deeply affected by the spacing between each fish in the school. When the horizontal separation is smaller than the length of the fish body, the downstream fish exhibits a larger thrust coefficient and greater propulsive efficiency than the isolated fish. However, the corresponding values for the upstream fish are smaller. The opposite behavior occurs when the horizontal separation increases beyond the length of fish body. The propulsive performance of the entire oblique school of fish can be substantially enhanced when the separations are optimized.展开更多
We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1 ...We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention (EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTX-loaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles (especially IC50 = 0.123 ± 0.035μmol/L of micelles and 0.298 ± 0.067μmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.展开更多
Pattern matching method is one of the classic classifications of existing online portfolio selection strategies. This article aims to study the key aspects of this method—measurement of similarity and selection of si...Pattern matching method is one of the classic classifications of existing online portfolio selection strategies. This article aims to study the key aspects of this method—measurement of similarity and selection of similarity sets, and proposes a Portfolio Selection Method based on Pattern Matching with Dual Information of Direction and Distance (PMDI). By studying different combination methods of indicators such as Euclidean distance, Chebyshev distance, and correlation coefficient, important information such as direction and distance in stock historical price information is extracted, thereby filtering out the similarity set required for pattern matching based investment portfolio selection algorithms. A large number of experiments conducted on two datasets of real stock markets have shown that PMDI outperforms other algorithms in balancing income and risk. Therefore, it is suitable for the financial environment in the real world.展开更多
Orthodontic tooth movement(OTM)depends on periodontal ligament cells(PDLCs),which sense biomechanical stimuli and initiate alveolar bone remodeling.Light(optimal)forces accelerate OTM,whereas heavy forces decelerate i...Orthodontic tooth movement(OTM)depends on periodontal ligament cells(PDLCs),which sense biomechanical stimuli and initiate alveolar bone remodeling.Light(optimal)forces accelerate OTM,whereas heavy forces decelerate it.However,the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces(MFs)remain unclear.This study demonstrates that mechanosensitive ion channel Piezo1-medi-ated Ca^(2+)signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs un-der heavy-force conditions.Heavy MF up-regulated Piezo1 in PDLCs,reducing mitochondrial Ca^(2+)influx by inhibiting ITPR3 expression in mitochondria-associated membranes.Decreased mito-chondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS-STING signaling cascade,subsequently inhibiting monocyte-to-osteo-clast differentiation.Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM.These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling.This mechanism may be a potential therapeutic target for accelerating OTM.展开更多
The Intermediate-Range Nuclear Forces Treaty(INF Treaty)is a milestone in the history of arms control negotiations between the United States and the Soviet Union,but there are continuous disputes during its existence....The Intermediate-Range Nuclear Forces Treaty(INF Treaty)is a milestone in the history of arms control negotiations between the United States and the Soviet Union,but there are continuous disputes during its existence.From February 2,2019,the United States announced the suspension of its obligations under the INF Treaty and officially started the withdrawal process.On the same day,the Russian president also announced the suspension of implementation.The factors behind the successive withdrawal are complicated and are related to the development of the international arms control system in the future.This paper mainly focuses on the analysis of the reasons for the withdrawal by comparing the two sides under the same perspective through the levels of analysis.展开更多
The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T(CAR-T)cell therapy in diverse tumors.Conventional CARs employ an intracellular domain(ICD)from theζsub...The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T(CAR-T)cell therapy in diverse tumors.Conventional CARs employ an intracellular domain(ICD)from theζsubunit of CD3 as a signaling module,and it is largely unknown how alternative CD3 chains potentially contribute to CAR design.Here,we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.While these reconstituted CARs conferred sufficient antigen-specific cytolytic activity on equipped T cells,they elicited low tonic signal,ameliorated the exhaustion and promoted memory differentiation of these cells.Intriguingly,the CD3ε-derived ICD outperformed others in generation of CAR-T cells that produced minimized cytokines.Mechanistically,CD3ε-based CARs displayed a restrained cytomembrane expression on engineered T cells,which was ascribed to endoplasmic reticulum retention mediated by the carboxyl terminal basic residues.The present study demonstrated the applicability of CAR reconstitution using signaling modules from different CD3 subunits,and depicted a novel pattern of CAR expression that reduces cytokine release,thus paving a way for preparation of CAR-T cells displaying improved safety and persistence against diverse tumor antigens.展开更多
With the rapid development of multi-modal foundation models and the pursuit of artificial general intelligence(AGI),there is a growing need for corresponding evaluation systems.Systematic AGI evaluation requires tasks...With the rapid development of multi-modal foundation models and the pursuit of artificial general intelligence(AGI),there is a growing need for corresponding evaluation systems.Systematic AGI evaluation requires tasks that encompass a wide range of ability dimensions and difficulty levels.However,although many benchmarks exist,the field still lacks a quantification system to assess ability decompositions or difficulty levels.Here,we took the visual domain as a starting point and proposed an explainable system for task ability decomposition and difficulty level quantification of vision(TADDL-V).Using large language models,TADDL-V decomposed the visual abilities required for a given task and leveraged statistical data to map between ability sets and task difficulty levels.The estimated ability masses align with human intuition,and TADDL-V's task difficulty estimates are empirically validated against aggregated human comparisons of task difficulty.Furthermore,we proposed an AGI visual evaluation task set,AGI-V70,comprising 70 composite visual tasks that incorporate visual abilities across a broad spectrum of task difficulties.Together,TADDL-V serves as a prototype for ability decomposition and task difficulty level quantification,which are essential for future AGI evaluations.展开更多
Lithium-ion batteries generally suffer from sluggish charge/mass transfer capability at high rates and low temperatures.Herein,a partially modulated structure of T-Nb_(2) O_(5) is designed by heteroatom doping and vac...Lithium-ion batteries generally suffer from sluggish charge/mass transfer capability at high rates and low temperatures.Herein,a partially modulated structure of T-Nb_(2) O_(5) is designed by heteroatom doping and vacancy regulation to enhance low-temperature reaction kinetics.We find that the synergistic effect can shorten the band gap,regulate the electronic active states and broaden the lithium-ion diffusion channel,thereby increasing charge transport ability and accelerating low-temperature Li^(+) transport behavior.Meanwhile,the structure modification significantly reduces the lattice expansion from 3.98 to 4.06 Å during the repeated lithiation-delithiation process.Benefiting from the structural advantages,Zr_(0.05)-Nb_(2) O_(5) anode exhibits an excellent rate performance(136.9 m Ah g^(-1)at 20 C) and an impressive low-temperature cycle life with slight capacity degradation after 550 cycles at-30 ℃.A full cell with a LiNi_(0.5)Co_(0.2)Mn_(0.3)O_(2) cathode delivers capacity retention of 96.1% after 300 cycles at-30℃,demonstrating its practical feasibility.This work presents a novel concept to improve low-temperature charge transfer of T-Nb_(2) O_(5) for the development of long-life and fast-charging LIBs.展开更多
基金supported by the Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine(Grant No.2023-3HIM).
文摘Clostridioides difficile(C.difficile)is one of the major causes of nosocomial infections.Pregnant women,who are generally considered at low risk for C.difficile infection(CDI),have attracted attention because of an increasing number of reports.Oral vancomycin,the only first-line treatment for pregnant women infected with C.difficile,has been associated with increasing strain resistance,leading to decreased efficacy.Fecal microbiota transplantation(FMT)is recommended for severe,fulminant,and recurrent CDI;however,it is generally avoided in pregnant women because of safety concerns.We report a case of a pregnant woman with a primary ribotype 027 CDI who experienced a successful outcome with washed microbiota transplantation(WMT),an improved form of FMT,via enema.The specific strain of ribotype 027 is related to severe outcomes but has not previously been reported in pregnant women.The follow-up lasted for two years,during which the patient's diarrhea was fully alleviated without recurrence.The baby showed normal growth and development,and no adverse events were recorded for either.This case provides evidence for the efficacy and safety of WMT in pregnant women infected with C.difficile,indicating that WMT via enema may be a viable therapeutic strategy for this population for treating CDI.
基金This work was supported by the National Natural Science Foundation of China(Grants 11862017,11462015 and 61963029).
文摘The variable flexibility of a fish body is believed to play a significant role in improving swimming performance.To explore the effect of non-uniform flexibility on the motion performance of fish under biologically relevant conditions,we set up three different flexible distribution modes for a semi-free filament and compared the motion performance of different flexible distribution modes through numerical simulations.The filament is located in the wake of the front flapping foil;it can swing adaptively in the lateral direction according to the flow situation of the surrounding fluid and finally reach a stable position.The results show that the motion state of the filament will alter with a change in the flexibility of the filament,from moving in the vortex street to moving on the side of the vortex street.In the Bénard-von Kármán(BvK)vortex streets,the drag coefficient of the filament increases as the flexibility of the filament increases,and the value of the drag coefficient is at a minimum when the flexibility of the filament increases linearly along the length of the filament.Further investigation indicates that at 85%–90%of the filament length(starting from the leading edge),the flexibility of the filament begins to increase significantly,and the filament can obtain its best propulsion performance.The results of this work provide new insights into the role of non-uniform flexibility during the process of fish movement and provide a valuable reference for the design of bionic underwater vehicles.
文摘The hydrodynamics in fish school are studied through simulating the flow over two wiggling hydrofoils in diagonal arrangement by using the immersed boundary method, both in-phase and anti-phase wiggling motions are considered in this study, the effect of the longitudinal spacing on the hydrodynamic performance has been investigated. It is revealed that, when the longitudinal spacing is smaller than body length, the diagonal formation is helpful to the follower but harmful to the leader;when the longitudinal spacing is larger than body length, the opposite effect is occurring;and a significant enhancement of the propulsive performance is obtained when the longitudinal spacing is optimized.
基金the National Natural Science Foundation of China(Grant No.11862017).
文摘At low Reynolds numbers,the variable flexibility of flapping insect wings is considered essential in improving the favorable aerodynamic forces.To further explore whether significant aerodynamic coupling exists between the microstructure and passive flexible deformation,this paper proposes three technical comparison airfoils:a corrugated wing with deformation,a symmetric flat plate wing with deformation,and a corrugated wing without deformation.Based on STAR-CCM+software,this paper numerically solves the Navier-Stokes equations using the fluid-structure interaction method.The results show that the aerodynamic performance of the flexible corrugated wing is better than that of the rigid corrugated wing,and its lift and thrust are both improved to a certain extent,and the thrust efficiency of the flexible corrugated wing is significantly higher than that of the flexible flat plate.Although the thrust is improved,a part of the lift is lost,and as the flapping amplitude increases past 35°,the disparity gradually increases.A comparison of the flexible technical airfoils shows that the corrugated structure promotes thrust and retards lift,which is closely related to the formation and dissipation of strong vortex rings during the downstroke phase.On the premise of maintaining typical flapping without falling,dragonflies can fly with skillful efficiency by adjusting the way they flap their wings.The results of this work provide new insight into the formation and role of thrust in flapping maneuvering flight and provide a specific reference for developing new bionic flapping-wing aircraft.
基金National Natural Science Foundation of China(No.52077185)the Basic Research Program of Science and Technology of Shenzhen,China(No.JCYJ20190809162617137)for partial financial support+6 种基金the financial supports from the Basic Ability Promotion Project for Young and Middle-Aged Teachers in Universities of Guangxi(No.2018KY0083)Doctoral Scientific Research Fund of Guangxi Normal University(No.2017BQ019)the financial supports from National Natural Science Foundation of China(No.11975061)the Technology Innovation and Application Development Project of Chongqing(No.cstc2019jscxmsxm X0041)the Construction Committee Project of Chongqing(No.2018-1-3-6)the Fundamental Research Funds for the Central Universities(No.2019CDQYDQ034)the Australian Research Council(ARC)for partial support。
文摘The quantification of hydrogen peroxide(H_(2)O_(2))generated in the plasma-liquid interactions is of great importance,since the H_(2)O_(2)species is vital for the applications of the plasma-liquid system.Herein,we report on in situ quantification of the aqueous H_(2)O_(2)(H_(2)O_(2)aq)using a colorimetric method for the DC plasma-liquid systems with liquid as either a cathode or an anode.The results show that the H_(2)O_(2)aqyield is 8-12 times larger when the liquid acts as a cathode than when the liquid acts as an anode.The conversion rate of the gaseous OH radicals to H_(2)O_(2)aqis 4-6 times greater in the former case.However,the concentrations of dissolved OH radicals for both liquid as cathode and anode are of the same order of tens of n M.
文摘The vortex formation and organization are the key to understand the intrinsic mechanism in flying and swimming in nature. The vortex wake of dual-flapping foils is numerically investigated using the immersed boundary method. Beside the deflection of the reversed von-Kármán vortex street, an interesting phenomenon, the deflection of the von-Kármán vortex street, is observed behind the dual-flapping foils. The deflected direction is not according to the initial direction of biplane’s flapping motion. And the deflection angle is related to the difference between upward and downward deflecting velocities.
基金supported by the National Natural Science Foundation of China (Grant 11462015)
文摘The propulsive performance of an oblique school of fish is numerically studied using an immersed boundary technique. The effect of the spacing and wiggling phase on the hydrodynamics of the system is investigated. The hydrodynamics of the system is deeply affected by the spacing between each fish in the school. When the horizontal separation is smaller than the length of the fish body, the downstream fish exhibits a larger thrust coefficient and greater propulsive efficiency than the isolated fish. However, the corresponding values for the upstream fish are smaller. The opposite behavior occurs when the horizontal separation increases beyond the length of fish body. The propulsive performance of the entire oblique school of fish can be substantially enhanced when the separations are optimized.
基金supported by grants from the National Natural Science Foundation of China(No.81872733)the Natural Science Foundation of Jiangsu Province of China(No.15KJB310004)
文摘We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention (EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTX-loaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles (especially IC50 = 0.123 ± 0.035μmol/L of micelles and 0.298 ± 0.067μmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.
基金This work was supported by Basic Science Center Program of the National Natural Science Foundation of China for"Multiscale Problems in Nonlinear Mechanics"(Grant No.11988102)the National Natural Science Foundation of China(Grant Nos.12102439,92252203,and 91952301)the China Postdoctoral Science Foundation(Grant No.2021M703290)。
文摘Pattern matching method is one of the classic classifications of existing online portfolio selection strategies. This article aims to study the key aspects of this method—measurement of similarity and selection of similarity sets, and proposes a Portfolio Selection Method based on Pattern Matching with Dual Information of Direction and Distance (PMDI). By studying different combination methods of indicators such as Euclidean distance, Chebyshev distance, and correlation coefficient, important information such as direction and distance in stock historical price information is extracted, thereby filtering out the similarity set required for pattern matching based investment portfolio selection algorithms. A large number of experiments conducted on two datasets of real stock markets have shown that PMDI outperforms other algorithms in balancing income and risk. Therefore, it is suitable for the financial environment in the real world.
基金supported by the Natural Science Foundation of China (No.82471016,81470772)Chongqing Talent Program:Innovative Leading Talents (Medical Field,No.CQYC20210303384)+1 种基金Chongqing Medical Scientific Research Project (China) (No.cstc2020jcyj-msxmX0307)Youth Innovation in Future Medicine (Chongqing Medical University) (No.W0033).
文摘Orthodontic tooth movement(OTM)depends on periodontal ligament cells(PDLCs),which sense biomechanical stimuli and initiate alveolar bone remodeling.Light(optimal)forces accelerate OTM,whereas heavy forces decelerate it.However,the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces(MFs)remain unclear.This study demonstrates that mechanosensitive ion channel Piezo1-medi-ated Ca^(2+)signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs un-der heavy-force conditions.Heavy MF up-regulated Piezo1 in PDLCs,reducing mitochondrial Ca^(2+)influx by inhibiting ITPR3 expression in mitochondria-associated membranes.Decreased mito-chondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS-STING signaling cascade,subsequently inhibiting monocyte-to-osteo-clast differentiation.Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM.These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling.This mechanism may be a potential therapeutic target for accelerating OTM.
文摘The Intermediate-Range Nuclear Forces Treaty(INF Treaty)is a milestone in the history of arms control negotiations between the United States and the Soviet Union,but there are continuous disputes during its existence.From February 2,2019,the United States announced the suspension of its obligations under the INF Treaty and officially started the withdrawal process.On the same day,the Russian president also announced the suspension of implementation.The factors behind the successive withdrawal are complicated and are related to the development of the international arms control system in the future.This paper mainly focuses on the analysis of the reasons for the withdrawal by comparing the two sides under the same perspective through the levels of analysis.
基金supported by funding from the National Natural Science Foundation of China(81630069,81972870&82172910)the Shaanxi Innovative Research Team for Key Science and Technology(S2022-ZC-TD-0065).
文摘The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T(CAR-T)cell therapy in diverse tumors.Conventional CARs employ an intracellular domain(ICD)from theζsubunit of CD3 as a signaling module,and it is largely unknown how alternative CD3 chains potentially contribute to CAR design.Here,we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.While these reconstituted CARs conferred sufficient antigen-specific cytolytic activity on equipped T cells,they elicited low tonic signal,ameliorated the exhaustion and promoted memory differentiation of these cells.Intriguingly,the CD3ε-derived ICD outperformed others in generation of CAR-T cells that produced minimized cytokines.Mechanistically,CD3ε-based CARs displayed a restrained cytomembrane expression on engineered T cells,which was ascribed to endoplasmic reticulum retention mediated by the carboxyl terminal basic residues.The present study demonstrated the applicability of CAR reconstitution using signaling modules from different CD3 subunits,and depicted a novel pattern of CAR expression that reduces cytokine release,thus paving a way for preparation of CAR-T cells displaying improved safety and persistence against diverse tumor antigens.
基金supported by the National Science and Technology Major Project(Grant No.2022ZD0114900)the National Natural Science Foundation of China(Grant Nos.32471151,32200854)the Young Elite Scientists Sponsorship Program(Grant No.2021QNRC00)to Yujia PENG。
文摘With the rapid development of multi-modal foundation models and the pursuit of artificial general intelligence(AGI),there is a growing need for corresponding evaluation systems.Systematic AGI evaluation requires tasks that encompass a wide range of ability dimensions and difficulty levels.However,although many benchmarks exist,the field still lacks a quantification system to assess ability decompositions or difficulty levels.Here,we took the visual domain as a starting point and proposed an explainable system for task ability decomposition and difficulty level quantification of vision(TADDL-V).Using large language models,TADDL-V decomposed the visual abilities required for a given task and leveraged statistical data to map between ability sets and task difficulty levels.The estimated ability masses align with human intuition,and TADDL-V's task difficulty estimates are empirically validated against aggregated human comparisons of task difficulty.Furthermore,we proposed an AGI visual evaluation task set,AGI-V70,comprising 70 composite visual tasks that incorporate visual abilities across a broad spectrum of task difficulties.Together,TADDL-V serves as a prototype for ability decomposition and task difficulty level quantification,which are essential for future AGI evaluations.
基金supported by the National Natural Science Foundation of China (22279026,2247090373)the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX1401)+2 种基金the Major Science and Technology Projects for Independent Innovation of China FAW Group Co.,Ltd.the Fundamental Research Funds for the Central Universities (HIT.OCEF.2022017)the China Postdoctoral Science Foundation (2024M764198)。
文摘Lithium-ion batteries generally suffer from sluggish charge/mass transfer capability at high rates and low temperatures.Herein,a partially modulated structure of T-Nb_(2) O_(5) is designed by heteroatom doping and vacancy regulation to enhance low-temperature reaction kinetics.We find that the synergistic effect can shorten the band gap,regulate the electronic active states and broaden the lithium-ion diffusion channel,thereby increasing charge transport ability and accelerating low-temperature Li^(+) transport behavior.Meanwhile,the structure modification significantly reduces the lattice expansion from 3.98 to 4.06 Å during the repeated lithiation-delithiation process.Benefiting from the structural advantages,Zr_(0.05)-Nb_(2) O_(5) anode exhibits an excellent rate performance(136.9 m Ah g^(-1)at 20 C) and an impressive low-temperature cycle life with slight capacity degradation after 550 cycles at-30 ℃.A full cell with a LiNi_(0.5)Co_(0.2)Mn_(0.3)O_(2) cathode delivers capacity retention of 96.1% after 300 cycles at-30℃,demonstrating its practical feasibility.This work presents a novel concept to improve low-temperature charge transfer of T-Nb_(2) O_(5) for the development of long-life and fast-charging LIBs.
