mc211vm is a process-level ARM-to-x86 binary translator developed in our lab in the past several years. Currently, it is able to emulate singlethreaded programs. We extend mc211vm to emulate multi-threaded programs. O...mc211vm is a process-level ARM-to-x86 binary translator developed in our lab in the past several years. Currently, it is able to emulate singlethreaded programs. We extend mc211vm to emulate multi-threaded programs. Our main task is to reconstruct its architecture for multi-threaded programs. Register mapping, code cache management, and address mapping in mc2llvm have all been modified. In addition, to further speed up the emulation, we collect hot paths, aggressively optimize and generate code for them at run time. Additional threads are used to alleviate the overhead. Thus, when the same hot path is walked through again, the corresponding optimized native code will be executed instead. In our experiments, our system is 8.8X faster than QEMU (quick emulator) on average when emulating the specified benchmarks with 8 guest threads.展开更多
BACKGROUND Icariin(ICA)is a natural compound derived from Epimedium that has shown promise in treating colorectal cancer(CRC)by reducing inflammation,inducing apoptosis,and limiting tumor progression.AIM To elucidate ...BACKGROUND Icariin(ICA)is a natural compound derived from Epimedium that has shown promise in treating colorectal cancer(CRC)by reducing inflammation,inducing apoptosis,and limiting tumor progression.AIM To elucidate the specific mechanisms underlying its therapeutic effects on this malignancy.METHODS We examined the impact of different ICA concentrations on the biological behavior of CRC cells in vitro.We also assessed the protein expression of SMAD4,CX-C motif chemokine ligand 1(CXCL1),and CXCL8,as well as epithelial-mesenchymal transition(EMT)-related signaling molecules,and the mRNA expression of proinflammatory factors.To further explore ICA’s mechanisms in CRC treatment,we introduced small interfering SMAD4 and its negative control group.In CRC cells,we evaluated proliferation,apoptosis,invasion,migration,EMT,and the recruitment of tumor-associated neutrophils(TANs).Moreover,we investigated the role of the CXCL8-C-X-C motif chemokine receptor 2(CXCR2)axis in the recruitment of ICA-affected TANs.In vivo,we preliminarily assessed the therapeutic efficacy of ICA against CRC.In ICA-treated mice,we measured tumor size,histological morphology,apoptosis,and neutrophil infiltration.Additionally,we analyzed the expression of SMAD4,CXCL1,CXCL8,CXCR2,EMT,and proteins related to migration.RESULTS Our findings indicate that ICA attenuated CRC cell proliferation,invasion,and migration,while suppressing TAN recruitment and promoting apoptosis in a concentration-dependent manner.When small interfering SMAD4 was introduced,the anticancer effects of ICA were diminished.Furthermore,disruption of the CXCL8-CXCR2 axis reduced neutrophil recruitment.We found that ICA inhibited tumor growth,improved tumor histology and morphology,alleviated CD66b+neutrophil infiltration,and inhibited EMT in mice with subcutaneous CRC tumors.In addition,ICA appeared to enhance SMAD4 protein expression while suppressing CXCL8 and CXCR2 expression in both in vivo and in vitro experiments.CONCLUSION ICA impedes the recruitment of TANs primarily through SMAD4-mediated modulation of the CXCL8-CXCR2 axis,thereby suppressing EMT and other pro-metastatic programs in CRC.展开更多
Objective:Multiple programmed cell death(PCD)pathways have been individually reported to be triggered by cisplatin,but whether and how they are co-regulated remains unclear.In this study,we comprehensively investigate...Objective:Multiple programmed cell death(PCD)pathways have been individually reported to be triggered by cisplatin,but whether and how they are co-regulated remains unclear.In this study,we comprehensively investigate the spectrum of cisplatin-induced PCD.Methods:We employed integrated in vitro and in vivo models including human cancer cell lines,a Cal27 xenograft mouse model,and paired clinical specimens from an oral squamous cell carcinoma patient receiving neoadjuvant cisplatin-based chemotherapy.A comprehensive methodological suite-encompassing cell death assays,Western blotting,Hematoxylin and eosin staining,immunofluorescence,Cyclic multiplexed tissue staining,and pathway-specific pharmacological inhibitors was utilized to dissect the activation of apoptosis,necroptosis,pyroptosis,and ferroptosis.Results:Cisplatin simultaneously upregulates markers of PCD pathways(including apoptosis,necroptosis,pyroptosis,and ferroptosis)in a dose-or time-dependent manner.Pharmacological inhibition or genetic knockdown of key genes in each pathway significantly reduced cytotoxicity.confirming their functional roles.Notably,indicators of key pro-inflammatory death modalities,pyroptosis and ferroptosis,were prominently co-upregulated in both xenograft tumors and clinical patient samples,suggesting that these two forms of PCD may represent the predominant death forms in cisplatin-induced tumor cell death.Conclusion:Cisplatin induces the coordinated activation of multiple cell death programs within a unified framework.Prominent engagement of immunogenic cell death pathways,particularly pyroptosis and ferroptosis,provides a mechanistic basis for the clinically observed synergy between cisplatin and immune checkpoint blockade therapy.展开更多
Instrumental and expert assessments were used to assess the effect of massage on facial skin blood perfusion,as well as the effects of the long-term use of the two skin health programs on the water content of the stra...Instrumental and expert assessments were used to assess the effect of massage on facial skin blood perfusion,as well as the effects of the long-term use of the two skin health programs on the water content of the stratum corneum,F4,L*,dermal and epidermal thickness and density,facial wrinkles,and so on.Sixty healthy Chinese women were selected as the study subjects,which were subsequently divided into G1 non-massage group and G2 massage group.The results show that massage can increase the blood perfusion of facial skin.Group G2 solution is found to be more effective in improving the skin structural barrier(epidermal density),skin elasticity,firmness(dermal thickness)and forehead wrinkles.展开更多
Background Liver cancer is among the top five causes of cancer death in 90 countries,with China accounting for a substantial proportion of the global burden.This study aimed to analyse the national liver cancer polici...Background Liver cancer is among the top five causes of cancer death in 90 countries,with China accounting for a substantial proportion of the global burden.This study aimed to analyse the national liver cancer policies and programs in China.Methods This study applied a documentary research method using the systematic READ approach.Six national official websites and one public policy database were searched.The document analysis was based on the WHO Health System's Six Building Blocks and the WHO's four modules of cancer control(prevention,early detection,diagnosis and treatment,and palliative care).Results A total of 74 liver cancer-related policies and 8 programs published from 1 January 1984 to 31 March 2025 were included in this study.The analysis revealed that liver cancer management in China mainly focused on Medical products and Technologies(n=46,62.16%),and Service Delivery(n=34,45.95%)within the WHO health system building blocks.When it came to WHO cancer control four modules,most policies(n=39,52.70%)targeted Diagnosis and Treatment of liver cancer,followed by Prevention of liver cancer(n=33,44.59%).Additionally,8 national programs were implemented to improve the prevention,diagnosis,and treatment of liver cancer.Before 2019,the emphasis of liver cancer prevention was primarily on hepatitis prevention and control.However,since 2020,the national-level programs aimed at preventing and controlling liver cancer emphasizing patient education and treatment for high-risk groups.Conclusions China's liver cancer control mainly focused heavily on prevention,diagnosis and treatment modules with special focus on medical products and technology,as well as service delivery.Currently,less attention has been given to the detection and palliative care of survivors.The control of liver cancer in China still requires further strengthening of the health system for implementation.Considering the continual increase in the burden of liver cancer,it is imperative for future efforts to develop a comprehensive national liver cancer strategy.展开更多
During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive...During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h2/(4√2),where h is the piecewise length.展开更多
Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
This study introduces FTCSEM,a FORTRAN-based,parallelized one-dimensional controlledsource electromagnetic(CSEM)forward modeling and inversion software capable of accommodating arbitrary source-receiver confi guration...This study introduces FTCSEM,a FORTRAN-based,parallelized one-dimensional controlledsource electromagnetic(CSEM)forward modeling and inversion software capable of accommodating arbitrary source-receiver confi gurations.In comparison to existing one-dimensional CSEM tools,FTCSEM incorporates several signifi cant enhancements:it supports transmitters of diverse shapes,quantities,and spatial locations;permits receivers to be positioned flexibly on the surface,subsurface,or in the atmosphere;facilitates simulations and inversions in both frequency and time domains;integrates an adaptive regularized inversion algorithm with multiple model constraints;and leverages GPU-accelerated parallel computing to attain high computational efficiency.Validation through numerical experiments and field data inversion confirms the program’s accuracy and practical applicability.The findings indicate that FTCSEM performs robustly in complex geoelectric environments,multi-source and multi-receiver arrangements,as well as multi-component joint inversion scenarios,thereby offering a versatile and powerful tool for advancing CSEM research and applications.展开更多
Depression is a prevalent mental disorder characterized by persistent disinterest and a depressed mood,with severe cases potentially leading to suicide.In recent years,the incidence of depression has steadily increase...Depression is a prevalent mental disorder characterized by persistent disinterest and a depressed mood,with severe cases potentially leading to suicide.In recent years,the incidence of depression has steadily increased,making it the second-largest global health burden.The pathogenesis of depression involves a series of complex pathological mechanisms,although the key underlying causes remain unclear.Programmed cell death(PCD),including apoptosis,autophagy,pyroptosis,ferroptosis,and necroptosis,involves highly organized gene expression processes that may influence the occurrence and development of depression by regulating cellular fate.Furthermore,numerous studies have shown that natural products can modulate PCDs through various signaling pathways,presenting significant potential for managing depression.Natural products offer benefits such as cost-effectiveness,fewer side effects,and other advantages,making them viable supplements or alternatives to traditional antidepressant drugs.To explore this potential,we reviewed studies demonstrating the antidepressant effects of natural products through multi-target modulation of PCDs.In addition,we discussed the toxicity and clinical applications of these natural products.This study highlights that diverse core biological pathways and targets are involved in determining the fate of depression-associated brain cells,including the PI3K/Akt signaling pathway,caspase-8,GSDMD,and others.In conclusion,the multi-target mechanisms of PCD regulation by natural products may provide a promising foundation for the future development of novel antidepressant medications.展开更多
It is important for a lunar lander to possess a large divert capability during the final landing phase,as this can enhance the tolerance for flight deviations in the early phase or improve the obstacle avoidance perfo...It is important for a lunar lander to possess a large divert capability during the final landing phase,as this can enhance the tolerance for flight deviations in the early phase or improve the obstacle avoidance performance.Therefore,when designing the powered descent trajectory,sufficient final phase divert capability should be reserved at the minimum propellant cost.To this end,a multi-phase trajectory programming(MPTP)method for powered descent with approaching phase divert capability is proposed.First,the entire powered descent trajectory is divided into the main braking phase and the approaching phase.The main braking phase is responsible for dissipating the majority of the initial velocity.The approaching phase is responsible for safely and precisely flying toward the landing site.It is nominally a vertical descent trajectory and possesses equal divert capability in all horizontal directions.Then,a constant-thrust linear tangent guidance(LTG)accounting for the lunar curvature is designed for the main braking phase.For the approaching phase,a variable-thrust lossless convex programming(LCP)guidance considering the constraints of tilt angle and glide-slope angle is developed.Subsequently,to connect the two phases and further optimize the propellant consumption throughout the entire trajectory,a method for determining the phase switching condition is proposed.The originally difficult-to-solve two-parameter optimization problem is decomposed into two more easily solvable subproblems,which are solved iteratively via a bilevel optimization framework.Finally,the divert capability of the proposed method is verified through numerical simulation.The programmed trajectory is basically consistent with the results of the pseudospectral method,with the difference in propellant consumption being only 0.006%.This method is suitable for the rapid iterative design of nominal trajectories for lunar lander powered descent in engineering applications.展开更多
This paper delves into the H∞optimal output regulation problem for continuous-time linear systems with an unknown system model.By integrating the internal model principle with optimal control,we derive an optimal con...This paper delves into the H∞optimal output regulation problem for continuous-time linear systems with an unknown system model.By integrating the internal model principle with optimal control,we derive an optimal control policy and a worst-case disturbance policy through the formulation and solution of a zero-sum game problem.Subsequently,leveraging adaptive dynamic programming,we propose a policy iteration learning algorithm capable of learning both the optimal control policy and the worst-case disturbance policy directly from system data.The existing algorithms necessitate an initial stabilizing policy,a full-rank condition,and the storage of historical data to guarantee algorithm convergence.In contrast,we design a dual policy iteration algorithm equipped with an online learning mechanism,thereby eliminating these additional prerequisites.Simulation results with an antonomous ground vehicle underscore the effectiveness of our proposed algorithm,and its superiority is further demonstrated through comparisons with existing methodologies.展开更多
The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programmi...The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programming(LGP)has been developed for a full-scale annular ramjet combustor.The LGP is used to generate control laws that include multi-frequency forcing.These laws are then transformed into square waves to actuate the solenoid valve,which modulates the kerosene supply for open-loop control.The results show that the duty cycle has little effect on instability amplitude,whereas an increase in frequency leads to a remarked reduction in combustion amplitude.After five generations evolvements,the pressure amplitude is reduced by 40.6% under the optimal control law generated by LGP.Furthermore,the machine learning process is depicted using a proximity map of control law similarity,with the search pathway visualized by the steepest descent.All individuals go forward to the upper left corner of the map with the evolution process,terminating at the optimal individual of the fifth generation.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.展开更多
Natural convection in enclosures containing nanofluids has attracted significant attention due to its relevance in thermal management systems.In this context,this study presents a comprehensive numerical investigation...Natural convection in enclosures containing nanofluids has attracted significant attention due to its relevance in thermal management systems.In this context,this study presents a comprehensive numerical investigation of flow and heat transfer in a square cavity saturated with water-based CuO nanofluid having a centrally placed sinusoidal-shaped heated element.All the enclosure walls satisfy the no-slip velocity condition.Thermally,the vertical walls are kept at a cold reference temperature,the lower wall is partially heated at its center,and the remaining portions of the lower and entire upper walls are adiabatic.The internal sinusoidal element is also uniformly heated.The flow dynamics and thermal fields are governed by the two-dimensional steady-state Navier-Stokes and energy equations,solved using the Galerkin finite element method.Additionally,a novel hybrid approach integrating multi-expression programming(MEP)technique with a convolutional neural network bidirectional gated recurrent unit(CNN-BiGRU)deep learning network is also applied to enhance flow and thermal prediction accuracy.This hybrid approach enables precise evaluation of how heater waviness,magnetic field orientation,and nanoparticle dispersion influence flow structure and heat transfer.Results reveal stronger convection at high Rayleigh numbers,magnetic damping at increased Hartmann numbers,and higher temperatures with reduced velocity at greater nanoparticle concentrations.Among the analyzed situations,increasing heater waviness improves heat-transfer performance.Both the MEP and CNN-BiGRU models accurately capture the key features of flow and heat transport trends,indicating that the hybrid approach provides enhanced predictive capability for complex convection-driven nanofluid systems.展开更多
This paper proposes a hybrid sequential second-order cone programming(HSSOCP)method with a three-layer scheme for the entry trajectory optimization of the cross-domain morphing vehicles(CDMVs).By defining the new morp...This paper proposes a hybrid sequential second-order cone programming(HSSOCP)method with a three-layer scheme for the entry trajectory optimization of the cross-domain morphing vehicles(CDMVs).By defining the new morphing rate control variable and using relaxation techniques to relax the bank angle constraint,the SOCP-based entry problem is constructed.A dynamic relaxation penal-ization technique is developed in the first layer to overcome artificial infeasibility and significantly enhance initialization robustness.A novel standard oscillation identification(SOI)method is proposed to precisely identify the iteration oscillations of basic SSOCP in the second layer,which can significantly improve the solution accuracy.A soft-trust-region strategy is applied in the third layer to eliminate oscillations and accelerate convergence.Simulation results of two scenarios demonstrate that the proposed SOI method effectively avoids non-standard oscillation interference versus traditional methods.The morphing aircraft can complete tasks better with a 7.01%and 10.43%reduction in heat load respectively compared to fixed-wing aircraft.The HSSOCP method can maintain accuracy while reducing computation time by 63.47%and 73.86%versus VATSSOCP.Monte Carlo simulations further validate the robustness.展开更多
This paper develops an Oscillation-avoidance-based Multistage Trust-region Sequential Convex Programming(OMTSCP)method for the highly nonlinear entry trajectory optimization problem of Cross-Domain Morphing Vehicles(C...This paper develops an Oscillation-avoidance-based Multistage Trust-region Sequential Convex Programming(OMTSCP)method for the highly nonlinear entry trajectory optimization problem of Cross-Domain Morphing Vehicles(CDMVs).The decoupling of states and controls for complex nonlinear dynamics is achieved by defining new control and state variables.A series of sub convex problems is formulated by successive linearization and discretization of the constraints.The proposed Trust-region Sequential Convex Programming(TSCP)scheme consists of three stages:an initial guess generation stage,a basic solution stage,and an optimal solution stage.An approach to penalize the dynamic relaxation is firstly developed to obtain an initial guess with considerable accuracy and significantly improve the robustness of the algorithm by overcoming the drawbacks of potential artificial infeasibility.The oscillation phenomenon of the TSCP method under rectangular trust region is then investigated,and a novel N-shape-based oscillation identification method is proposed to identify the oscillation accurately.Finally,an oscillation-avoidance method based on the sort trust-region is proposed to improve the convergence of the TSCP algorithm.Numerical comparisons of the proposed method and a typical TSCP method,as well as the morphing and fixed-morphing vehicles are provided to demonstrate the effectiveness and efficiency of the proposed method and the performance advantages of the morphing vehicle.The robustness of the method is further verified by Monte Carlo simulation.展开更多
Gastric cancer(GC)remains one of the most common cancers and leading causes of cancer deaths globally1with 60.0%of cases and 56.6%of deaths occurring in East Asia.South Korea and Japan have conducted nationwide GC scr...Gastric cancer(GC)remains one of the most common cancers and leading causes of cancer deaths globally1with 60.0%of cases and 56.6%of deaths occurring in East Asia.South Korea and Japan have conducted nationwide GC screening programs for decades but with essential differences in strategies,organization,and coverage2.展开更多
BACKGROUND Pancreatic cancer(PC),a highly malignant gastrointestinal cancer,is generally diagnosed at an advanced stage.However,traditional therapies for advanced PC are limited and often unsuitable for older patients...BACKGROUND Pancreatic cancer(PC),a highly malignant gastrointestinal cancer,is generally diagnosed at an advanced stage.However,traditional therapies for advanced PC are limited and often unsuitable for older patients.AIM To identify clinical predictors in older patients with advanced PC to facilitate individualized treatment.METHODS This was a retrospective clinical analysis involving 99 patients aged≥65 years with advanced PC who received programmed death-1(PD-1)inhibitors at Ningbo Medical Center Lihuili Hospital from January 2019 to January 2025.Univariate and multivariate analyses were conducted to identify clinical predictors for survival outcomes,utilizing blood levels and other clinical information.RESULTS The median progression-free survival(PFS)was 4.6 months[95%confidence interval(CI):3.700-5.800],and the median overall survival(OS)was 6.5 months(95%CI:5.700-8.200).Multivariate analysis helped identify meaningful clinical differences in PFS and OS across subgroups,including factors such as Eastern Cooperative Oncology Group performance status,prognostic nutritional index,and triglyceride levels.Univariate analysis showed that factors such as the location of primary PC,carbohydrate antigen 199 levels,systemic immune-inflammation,neutrophil-to-lymphocyte ratio,and the combination therapy comprising PD-1 inhibitors and radiotherapy are of significant clinical relevance to both PFS and OS.CONCLUSION The treatment of advanced PC with PD-1 inhibitors presented several potential independent clinical predictive indicators of survival outcomes in older patients.This study highlighted the importance of pre-treatment clinical characteristics and hematological variables for predicting treatment outcomes in older patients with PC.展开更多
Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of...Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of choline can be induced by feeding rumen-protected choline(RPC)to beef cows during the periconceptional period.Results A preliminary experiment was conducted to determine changes in circulating concentrations of choline and its metabolites after RPC supplementation.Suckled beef cows were individually fed 0,30,60,and 90 g of RPC(i.e.,0,8.6,17.3 and 25.9 g choline chloride)and blood samples were collected at random times after feeding.There were no differences in plasma concentrations of choline or its metabolites between groups.In the second experiment,effects of feeding 60 g/d RPC from d-1 to 7 relative to timed artificial insemination were examined for suckled beef cows.Feeding RPC did not affect pregnancy or calving rates,pregnancy losses,plasma concentrations of pregnancy-associated glycoproteins,gestation length or calf birth weight.Calves from RPC fed dams were lighter than control calves at~118 days of age(range 75–150;age included in the statistical model)and at weaning at~248 days of age.There was no effect of treatment on hip height at~118 days of age although there was a trend for RPC calves to be shorter at weaning.Weight/height ratio was lower for RPC than control at both 118 and 248 days of age.Treatment did not affect testis weight at~118 days of age.Conclusions Supplementation of RPC during the periconceptional period programmed development to alter calf phenotype in the postnatal period.The net result,reduced body weight,was the opposite of the phenotype caused by the addition of choline to embryo culture medium.展开更多
Severe aortic stenosis has increased exponentially as a result of the aging of the population.Transcatheter aortic valve replacement(TAVR)procedures increase by 20%-30%per year in Spain.Referred patients are increasin...Severe aortic stenosis has increased exponentially as a result of the aging of the population.Transcatheter aortic valve replacement(TAVR)procedures increase by 20%-30%per year in Spain.Referred patients are increasingly older,have comorbidities,and frailty.TAVR cardiac rehabilitation(CR)programs significantly improve both functional capacity and quality of life of patients.However,there are no guidelines on how to carry out them and few elderly patients are referred to CR.Furthermore,mortality in women who undergo TAVR is higher than in men and even fewer are referred to CR programs.Multidisciplinary patient care,including comorbidities and frailty,is essential.It is necessary to ensure exquisite continuity of care during TAVR,CR,and the rest of the patient's life.Telerehabilitation could be an option in some lower-risk patients to include more patients in CR programs after TAVR,given the high demand.This article reviews the evidence on why CR should be performed in post-TAVR patients and proposes a practical and novel approach to the care process and the recommended aspects and components of the CR program.展开更多
基金supported by NSC under Grant No.NSC 100-2218-E-009-009MY3 and NSC 100-2218-E-009-010-MY3
摘要mc211vm is a process-level ARM-to-x86 binary translator developed in our lab in the past several years. Currently, it is able to emulate singlethreaded programs. We extend mc211vm to emulate multi-threaded programs. Our main task is to reconstruct its architecture for multi-threaded programs. Register mapping, code cache management, and address mapping in mc2llvm have all been modified. In addition, to further speed up the emulation, we collect hot paths, aggressively optimize and generate code for them at run time. Additional threads are used to alleviate the overhead. Thus, when the same hot path is walked through again, the corresponding optimized native code will be executed instead. In our experiments, our system is 8.8X faster than QEMU (quick emulator) on average when emulating the specified benchmarks with 8 guest threads.
摘要BACKGROUND Icariin(ICA)is a natural compound derived from Epimedium that has shown promise in treating colorectal cancer(CRC)by reducing inflammation,inducing apoptosis,and limiting tumor progression.AIM To elucidate the specific mechanisms underlying its therapeutic effects on this malignancy.METHODS We examined the impact of different ICA concentrations on the biological behavior of CRC cells in vitro.We also assessed the protein expression of SMAD4,CX-C motif chemokine ligand 1(CXCL1),and CXCL8,as well as epithelial-mesenchymal transition(EMT)-related signaling molecules,and the mRNA expression of proinflammatory factors.To further explore ICA’s mechanisms in CRC treatment,we introduced small interfering SMAD4 and its negative control group.In CRC cells,we evaluated proliferation,apoptosis,invasion,migration,EMT,and the recruitment of tumor-associated neutrophils(TANs).Moreover,we investigated the role of the CXCL8-C-X-C motif chemokine receptor 2(CXCR2)axis in the recruitment of ICA-affected TANs.In vivo,we preliminarily assessed the therapeutic efficacy of ICA against CRC.In ICA-treated mice,we measured tumor size,histological morphology,apoptosis,and neutrophil infiltration.Additionally,we analyzed the expression of SMAD4,CXCL1,CXCL8,CXCR2,EMT,and proteins related to migration.RESULTS Our findings indicate that ICA attenuated CRC cell proliferation,invasion,and migration,while suppressing TAN recruitment and promoting apoptosis in a concentration-dependent manner.When small interfering SMAD4 was introduced,the anticancer effects of ICA were diminished.Furthermore,disruption of the CXCL8-CXCR2 axis reduced neutrophil recruitment.We found that ICA inhibited tumor growth,improved tumor histology and morphology,alleviated CD66b+neutrophil infiltration,and inhibited EMT in mice with subcutaneous CRC tumors.In addition,ICA appeared to enhance SMAD4 protein expression while suppressing CXCL8 and CXCR2 expression in both in vivo and in vitro experiments.CONCLUSION ICA impedes the recruitment of TANs primarily through SMAD4-mediated modulation of the CXCL8-CXCR2 axis,thereby suppressing EMT and other pro-metastatic programs in CRC.
基金supported by the grants of the National Natural Science Foundations of China(NSFCGrant Nos.82170971,82373187,82273165)+2 种基金the Sichuan Science and Technology Program(Grant Nos.2025NSFJQ0062 and 2024YFFK0293)the Scientific Research Foundation of the West China Hospital of Stomatology,Sichuan University(RD-03-202110)the Special Funding for the State Key Laboratory of Oral Diseases,Sichuan University(SKLOD-2025KP009).
摘要Objective:Multiple programmed cell death(PCD)pathways have been individually reported to be triggered by cisplatin,but whether and how they are co-regulated remains unclear.In this study,we comprehensively investigate the spectrum of cisplatin-induced PCD.Methods:We employed integrated in vitro and in vivo models including human cancer cell lines,a Cal27 xenograft mouse model,and paired clinical specimens from an oral squamous cell carcinoma patient receiving neoadjuvant cisplatin-based chemotherapy.A comprehensive methodological suite-encompassing cell death assays,Western blotting,Hematoxylin and eosin staining,immunofluorescence,Cyclic multiplexed tissue staining,and pathway-specific pharmacological inhibitors was utilized to dissect the activation of apoptosis,necroptosis,pyroptosis,and ferroptosis.Results:Cisplatin simultaneously upregulates markers of PCD pathways(including apoptosis,necroptosis,pyroptosis,and ferroptosis)in a dose-or time-dependent manner.Pharmacological inhibition or genetic knockdown of key genes in each pathway significantly reduced cytotoxicity.confirming their functional roles.Notably,indicators of key pro-inflammatory death modalities,pyroptosis and ferroptosis,were prominently co-upregulated in both xenograft tumors and clinical patient samples,suggesting that these two forms of PCD may represent the predominant death forms in cisplatin-induced tumor cell death.Conclusion:Cisplatin induces the coordinated activation of multiple cell death programs within a unified framework.Prominent engagement of immunogenic cell death pathways,particularly pyroptosis and ferroptosis,provides a mechanistic basis for the clinically observed synergy between cisplatin and immune checkpoint blockade therapy.
摘要Instrumental and expert assessments were used to assess the effect of massage on facial skin blood perfusion,as well as the effects of the long-term use of the two skin health programs on the water content of the stratum corneum,F4,L*,dermal and epidermal thickness and density,facial wrinkles,and so on.Sixty healthy Chinese women were selected as the study subjects,which were subsequently divided into G1 non-massage group and G2 massage group.The results show that massage can increase the blood perfusion of facial skin.Group G2 solution is found to be more effective in improving the skin structural barrier(epidermal density),skin elasticity,firmness(dermal thickness)and forehead wrinkles.
基金supported by the funding of the University of Macao(MYRGGRG2023-00059-ICMS)the Science and Technology Development Fund,Macao SAR(File No.0014/2023/AKP).
摘要Background Liver cancer is among the top five causes of cancer death in 90 countries,with China accounting for a substantial proportion of the global burden.This study aimed to analyse the national liver cancer policies and programs in China.Methods This study applied a documentary research method using the systematic READ approach.Six national official websites and one public policy database were searched.The document analysis was based on the WHO Health System's Six Building Blocks and the WHO's four modules of cancer control(prevention,early detection,diagnosis and treatment,and palliative care).Results A total of 74 liver cancer-related policies and 8 programs published from 1 January 1984 to 31 March 2025 were included in this study.The analysis revealed that liver cancer management in China mainly focused on Medical products and Technologies(n=46,62.16%),and Service Delivery(n=34,45.95%)within the WHO health system building blocks.When it came to WHO cancer control four modules,most policies(n=39,52.70%)targeted Diagnosis and Treatment of liver cancer,followed by Prevention of liver cancer(n=33,44.59%).Additionally,8 national programs were implemented to improve the prevention,diagnosis,and treatment of liver cancer.Before 2019,the emphasis of liver cancer prevention was primarily on hepatitis prevention and control.However,since 2020,the national-level programs aimed at preventing and controlling liver cancer emphasizing patient education and treatment for high-risk groups.Conclusions China's liver cancer control mainly focused heavily on prevention,diagnosis and treatment modules with special focus on medical products and technology,as well as service delivery.Currently,less attention has been given to the detection and palliative care of survivors.The control of liver cancer in China still requires further strengthening of the health system for implementation.Considering the continual increase in the burden of liver cancer,it is imperative for future efforts to develop a comprehensive national liver cancer strategy.
基金supported by the National Natural Sci‐ence Foundation of China(Grant No.62306325)。
摘要During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h2/(4√2),where h is the piecewise length.
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
摘要Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
基金funded by the National Natural Science Foundation of China(42274192 and 42030106)Youth Innovation Promotion Association CAS(2023070).
摘要This study introduces FTCSEM,a FORTRAN-based,parallelized one-dimensional controlledsource electromagnetic(CSEM)forward modeling and inversion software capable of accommodating arbitrary source-receiver confi gurations.In comparison to existing one-dimensional CSEM tools,FTCSEM incorporates several signifi cant enhancements:it supports transmitters of diverse shapes,quantities,and spatial locations;permits receivers to be positioned flexibly on the surface,subsurface,or in the atmosphere;facilitates simulations and inversions in both frequency and time domains;integrates an adaptive regularized inversion algorithm with multiple model constraints;and leverages GPU-accelerated parallel computing to attain high computational efficiency.Validation through numerical experiments and field data inversion confirms the program’s accuracy and practical applicability.The findings indicate that FTCSEM performs robustly in complex geoelectric environments,multi-source and multi-receiver arrangements,as well as multi-component joint inversion scenarios,thereby offering a versatile and powerful tool for advancing CSEM research and applications.
基金supported by the National Key Research and Development Program“Traditional Chinese Medicine Modernization Research”Key Project(Project No.:2018YFC1707500)Shandong Province Special Disease Prevention Project of Integrated Traditional Chinese and Western Medicine(Project No.:YXH2019ZXY006)Postdoctoral Fellowship Program of CPSF(Program No.:GZB20240036).
摘要Depression is a prevalent mental disorder characterized by persistent disinterest and a depressed mood,with severe cases potentially leading to suicide.In recent years,the incidence of depression has steadily increased,making it the second-largest global health burden.The pathogenesis of depression involves a series of complex pathological mechanisms,although the key underlying causes remain unclear.Programmed cell death(PCD),including apoptosis,autophagy,pyroptosis,ferroptosis,and necroptosis,involves highly organized gene expression processes that may influence the occurrence and development of depression by regulating cellular fate.Furthermore,numerous studies have shown that natural products can modulate PCDs through various signaling pathways,presenting significant potential for managing depression.Natural products offer benefits such as cost-effectiveness,fewer side effects,and other advantages,making them viable supplements or alternatives to traditional antidepressant drugs.To explore this potential,we reviewed studies demonstrating the antidepressant effects of natural products through multi-target modulation of PCDs.In addition,we discussed the toxicity and clinical applications of these natural products.This study highlights that diverse core biological pathways and targets are involved in determining the fate of depression-associated brain cells,including the PI3K/Akt signaling pathway,caspase-8,GSDMD,and others.In conclusion,the multi-target mechanisms of PCD regulation by natural products may provide a promising foundation for the future development of novel antidepressant medications.
基金Fourth Phase of the China's Lunar Exploration ProgramChina National Space Administration (D040103)+1 种基金National Natural Science Foundation of China (62394354)National Key Research and Development Program of China (2025YFF0513303).
摘要It is important for a lunar lander to possess a large divert capability during the final landing phase,as this can enhance the tolerance for flight deviations in the early phase or improve the obstacle avoidance performance.Therefore,when designing the powered descent trajectory,sufficient final phase divert capability should be reserved at the minimum propellant cost.To this end,a multi-phase trajectory programming(MPTP)method for powered descent with approaching phase divert capability is proposed.First,the entire powered descent trajectory is divided into the main braking phase and the approaching phase.The main braking phase is responsible for dissipating the majority of the initial velocity.The approaching phase is responsible for safely and precisely flying toward the landing site.It is nominally a vertical descent trajectory and possesses equal divert capability in all horizontal directions.Then,a constant-thrust linear tangent guidance(LTG)accounting for the lunar curvature is designed for the main braking phase.For the approaching phase,a variable-thrust lossless convex programming(LCP)guidance considering the constraints of tilt angle and glide-slope angle is developed.Subsequently,to connect the two phases and further optimize the propellant consumption throughout the entire trajectory,a method for determining the phase switching condition is proposed.The originally difficult-to-solve two-parameter optimization problem is decomposed into two more easily solvable subproblems,which are solved iteratively via a bilevel optimization framework.Finally,the divert capability of the proposed method is verified through numerical simulation.The programmed trajectory is basically consistent with the results of the pseudospectral method,with the difference in propellant consumption being only 0.006%.This method is suitable for the rapid iterative design of nominal trajectories for lunar lander powered descent in engineering applications.
基金supported by the National Natural Science Foundation of China(62322305,62495090,62495095)。
摘要This paper delves into the H∞optimal output regulation problem for continuous-time linear systems with an unknown system model.By integrating the internal model principle with optimal control,we derive an optimal control policy and a worst-case disturbance policy through the formulation and solution of a zero-sum game problem.Subsequently,leveraging adaptive dynamic programming,we propose a policy iteration learning algorithm capable of learning both the optimal control policy and the worst-case disturbance policy directly from system data.The existing algorithms necessitate an initial stabilizing policy,a full-rank condition,and the storage of historical data to guarantee algorithm convergence.In contrast,we design a dual policy iteration algorithm equipped with an online learning mechanism,thereby eliminating these additional prerequisites.Simulation results with an antonomous ground vehicle underscore the effectiveness of our proposed algorithm,and its superiority is further demonstrated through comparisons with existing methodologies.
基金support from the National Natural Science Foundation of China(No.12002372)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2022QNRC001)the Natural Science Foundation of Hunan Province,China(No.2021JJ40674)。
摘要The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programming(LGP)has been developed for a full-scale annular ramjet combustor.The LGP is used to generate control laws that include multi-frequency forcing.These laws are then transformed into square waves to actuate the solenoid valve,which modulates the kerosene supply for open-loop control.The results show that the duty cycle has little effect on instability amplitude,whereas an increase in frequency leads to a remarked reduction in combustion amplitude.After five generations evolvements,the pressure amplitude is reduced by 40.6% under the optimal control law generated by LGP.Furthermore,the machine learning process is depicted using a proximity map of control law similarity,with the search pathway visualized by the steepest descent.All individuals go forward to the upper left corner of the map with the evolution process,terminating at the optimal individual of the fifth generation.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
摘要The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
摘要Natural convection in enclosures containing nanofluids has attracted significant attention due to its relevance in thermal management systems.In this context,this study presents a comprehensive numerical investigation of flow and heat transfer in a square cavity saturated with water-based CuO nanofluid having a centrally placed sinusoidal-shaped heated element.All the enclosure walls satisfy the no-slip velocity condition.Thermally,the vertical walls are kept at a cold reference temperature,the lower wall is partially heated at its center,and the remaining portions of the lower and entire upper walls are adiabatic.The internal sinusoidal element is also uniformly heated.The flow dynamics and thermal fields are governed by the two-dimensional steady-state Navier-Stokes and energy equations,solved using the Galerkin finite element method.Additionally,a novel hybrid approach integrating multi-expression programming(MEP)technique with a convolutional neural network bidirectional gated recurrent unit(CNN-BiGRU)deep learning network is also applied to enhance flow and thermal prediction accuracy.This hybrid approach enables precise evaluation of how heater waviness,magnetic field orientation,and nanoparticle dispersion influence flow structure and heat transfer.Results reveal stronger convection at high Rayleigh numbers,magnetic damping at increased Hartmann numbers,and higher temperatures with reduced velocity at greater nanoparticle concentrations.Among the analyzed situations,increasing heater waviness improves heat-transfer performance.Both the MEP and CNN-BiGRU models accurately capture the key features of flow and heat transport trends,indicating that the hybrid approach provides enhanced predictive capability for complex convection-driven nanofluid systems.
基金supported by the Open Fund of Laboratory of Aerospace Servo Actuation and Transmission(No.LASAT-2022-A03).
摘要This paper proposes a hybrid sequential second-order cone programming(HSSOCP)method with a three-layer scheme for the entry trajectory optimization of the cross-domain morphing vehicles(CDMVs).By defining the new morphing rate control variable and using relaxation techniques to relax the bank angle constraint,the SOCP-based entry problem is constructed.A dynamic relaxation penal-ization technique is developed in the first layer to overcome artificial infeasibility and significantly enhance initialization robustness.A novel standard oscillation identification(SOI)method is proposed to precisely identify the iteration oscillations of basic SSOCP in the second layer,which can significantly improve the solution accuracy.A soft-trust-region strategy is applied in the third layer to eliminate oscillations and accelerate convergence.Simulation results of two scenarios demonstrate that the proposed SOI method effectively avoids non-standard oscillation interference versus traditional methods.The morphing aircraft can complete tasks better with a 7.01%and 10.43%reduction in heat load respectively compared to fixed-wing aircraft.The HSSOCP method can maintain accuracy while reducing computation time by 63.47%and 73.86%versus VATSSOCP.Monte Carlo simulations further validate the robustness.
基金supported by the Open Fund of Laboratory of Aerospace Servo Actuation and Transmission,China(No.LASAT-2022-A03)。
摘要This paper develops an Oscillation-avoidance-based Multistage Trust-region Sequential Convex Programming(OMTSCP)method for the highly nonlinear entry trajectory optimization problem of Cross-Domain Morphing Vehicles(CDMVs).The decoupling of states and controls for complex nonlinear dynamics is achieved by defining new control and state variables.A series of sub convex problems is formulated by successive linearization and discretization of the constraints.The proposed Trust-region Sequential Convex Programming(TSCP)scheme consists of three stages:an initial guess generation stage,a basic solution stage,and an optimal solution stage.An approach to penalize the dynamic relaxation is firstly developed to obtain an initial guess with considerable accuracy and significantly improve the robustness of the algorithm by overcoming the drawbacks of potential artificial infeasibility.The oscillation phenomenon of the TSCP method under rectangular trust region is then investigated,and a novel N-shape-based oscillation identification method is proposed to identify the oscillation accurately.Finally,an oscillation-avoidance method based on the sort trust-region is proposed to improve the convergence of the TSCP algorithm.Numerical comparisons of the proposed method and a typical TSCP method,as well as the morphing and fixed-morphing vehicles are provided to demonstrate the effectiveness and efficiency of the proposed method and the performance advantages of the morphing vehicle.The robustness of the method is further verified by Monte Carlo simulation.
基金supported by grants from the Shanghai Key Disciplines of Public Health(2023-2025)for New Threeyear Action Plan(Grant Nos.GWVI-11.1-22 and GWVI-11.1-23)the Fudan School of Public Health-Jiading CDC key disciplines for the high-quality development of public health(Grant No.GWGZLXK-2023-02)the Fudan Undergraduate Research Opportunities Program(Grant No.FDUROP-24647)。
摘要Gastric cancer(GC)remains one of the most common cancers and leading causes of cancer deaths globally1with 60.0%of cases and 56.6%of deaths occurring in East Asia.South Korea and Japan have conducted nationwide GC screening programs for decades but with essential differences in strategies,organization,and coverage2.
摘要BACKGROUND Pancreatic cancer(PC),a highly malignant gastrointestinal cancer,is generally diagnosed at an advanced stage.However,traditional therapies for advanced PC are limited and often unsuitable for older patients.AIM To identify clinical predictors in older patients with advanced PC to facilitate individualized treatment.METHODS This was a retrospective clinical analysis involving 99 patients aged≥65 years with advanced PC who received programmed death-1(PD-1)inhibitors at Ningbo Medical Center Lihuili Hospital from January 2019 to January 2025.Univariate and multivariate analyses were conducted to identify clinical predictors for survival outcomes,utilizing blood levels and other clinical information.RESULTS The median progression-free survival(PFS)was 4.6 months[95%confidence interval(CI):3.700-5.800],and the median overall survival(OS)was 6.5 months(95%CI:5.700-8.200).Multivariate analysis helped identify meaningful clinical differences in PFS and OS across subgroups,including factors such as Eastern Cooperative Oncology Group performance status,prognostic nutritional index,and triglyceride levels.Univariate analysis showed that factors such as the location of primary PC,carbohydrate antigen 199 levels,systemic immune-inflammation,neutrophil-to-lymphocyte ratio,and the combination therapy comprising PD-1 inhibitors and radiotherapy are of significant clinical relevance to both PFS and OS.CONCLUSION The treatment of advanced PC with PD-1 inhibitors presented several potential independent clinical predictive indicators of survival outcomes in older patients.This study highlighted the importance of pre-treatment clinical characteristics and hematological variables for predicting treatment outcomes in older patients with PC.
基金supported by the L.E.“Red”Larson Endowment and grants number 2020-67015-30821 and 2023-67015-40730 from the Agriculture and Food Research Initiative of USDA-NIFAsupported by the Higher Education Commission of Pakistan。
摘要Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of choline can be induced by feeding rumen-protected choline(RPC)to beef cows during the periconceptional period.Results A preliminary experiment was conducted to determine changes in circulating concentrations of choline and its metabolites after RPC supplementation.Suckled beef cows were individually fed 0,30,60,and 90 g of RPC(i.e.,0,8.6,17.3 and 25.9 g choline chloride)and blood samples were collected at random times after feeding.There were no differences in plasma concentrations of choline or its metabolites between groups.In the second experiment,effects of feeding 60 g/d RPC from d-1 to 7 relative to timed artificial insemination were examined for suckled beef cows.Feeding RPC did not affect pregnancy or calving rates,pregnancy losses,plasma concentrations of pregnancy-associated glycoproteins,gestation length or calf birth weight.Calves from RPC fed dams were lighter than control calves at~118 days of age(range 75–150;age included in the statistical model)and at weaning at~248 days of age.There was no effect of treatment on hip height at~118 days of age although there was a trend for RPC calves to be shorter at weaning.Weight/height ratio was lower for RPC than control at both 118 and 248 days of age.Treatment did not affect testis weight at~118 days of age.Conclusions Supplementation of RPC during the periconceptional period programmed development to alter calf phenotype in the postnatal period.The net result,reduced body weight,was the opposite of the phenotype caused by the addition of choline to embryo culture medium.
摘要Severe aortic stenosis has increased exponentially as a result of the aging of the population.Transcatheter aortic valve replacement(TAVR)procedures increase by 20%-30%per year in Spain.Referred patients are increasingly older,have comorbidities,and frailty.TAVR cardiac rehabilitation(CR)programs significantly improve both functional capacity and quality of life of patients.However,there are no guidelines on how to carry out them and few elderly patients are referred to CR.Furthermore,mortality in women who undergo TAVR is higher than in men and even fewer are referred to CR programs.Multidisciplinary patient care,including comorbidities and frailty,is essential.It is necessary to ensure exquisite continuity of care during TAVR,CR,and the rest of the patient's life.Telerehabilitation could be an option in some lower-risk patients to include more patients in CR programs after TAVR,given the high demand.This article reviews the evidence on why CR should be performed in post-TAVR patients and proposes a practical and novel approach to the care process and the recommended aspects and components of the CR program.