Scientific understanding of the trade-offs between services is crucial for the scientific management and protection of ecosystems and the formulation of resource management policies.This study integrated meteorologica...Scientific understanding of the trade-offs between services is crucial for the scientific management and protection of ecosystems and the formulation of resource management policies.This study integrated meteorological,land use,and soil data to assess the ecosystem services,namely,water yield(WY),soil erosion(SE),and carbon sinks(CS),in peak-cluster depression basins on the Sino-Vietnamese border in China during 2000-2020.It analyzed the trade-offs and synergistic relationships among the three ecosystem services and their time-lag effects and driving mechanisms with the help of pixel-by-pixel time-lag intercorrelation and geographical de-tector methods.Results show that:1)from 2000 to 2020,the key ecosystem service indicators in the peak-cluster depression basins on the Sino-Vietnamese border in China demonstrated a significant and synergistic trend of positive change.The WY increased at a rate of 11.99 mm/yr,CS increased at a rate of 2.44 g C/(m^(2)∙yr),and SE decreased at a rate of 0.06 t/(ha∙yr).2)Most areas showed a synergistic relationship across the three ecosystem services,and the areas with a trade-off relationship were mostly concentrated in Baise City and the southwest of Chongzuo City,Guangxi.3)The time-lag effect between SE and WY was mostly concentrated in 0 yr,that between SE and CS was mostly concentrated in 5 yr,and that between CS and WY was mostly concentrated in 1 yr.4)Population density was the controlling factor between SE and WY.Vegetation coverage factor is the main controlling factor between SE and CS.The lithologic factor is the main controlling factor between CS and WY.Studying the trade-off relationship of ecosystem services at spatial and tem-poral scales on the Sino-Vietnamese border in China karst areas can provide a basis for regional ecological construction and develop-ment strategies,and it is conducive to meeting regional interest needs,maximizing comprehensive benefits,balancing the ecological en-vironment,and achieving regional sustainable development.展开更多
Most terrestrial models synchronously calculate net primary productivity(NPP)using the input climate variable,without the consideration of time-lag effects,which may increase the uncertainty of NPP simulation.Based on...Most terrestrial models synchronously calculate net primary productivity(NPP)using the input climate variable,without the consideration of time-lag effects,which may increase the uncertainty of NPP simulation.Based on Normalized Difference Vegetation Index(NDVI)and climate data,we used the time lag cross-correlation method to investigate the time-lag effects of temperature,precipitation,and solar radiation in different seasons on NDVI values.Then,we selected the Carnegie-Ames-Stanford approach(CASA)model to estimate the NPP of China from 2002 to 2017.The results showed that the response of vegetation growth to climate factors had an obvious lag effect,with the longest time lag in solar radiation and the shortest time lag in temperature.The time lag of vegetation to the climate variable showed great tempo-spatial heterogeneities among vegetation types,climate types,and vegetation growth periods.Based on the validation using eddy covariance data,the results showed that the simulation accuracy of the CASA model considering the time-lag effects was effectively improved.By considering the time-lag effects,the average total amount of NPP modeled by CASA during 2001-2017 in China was 3.977 PgC a^(−1),which is 11.37%higher than that of the original model.This study highlights the importance of considering the time lag for the simulation of vegetation growth,and provides a useful tool for the improvement of the vegetation productivity model.展开更多
The daily intake of total dietary fiber (TDF) was evaluated from data of the National Nutrition Survey (NNS) in Japan for 41 years since 1947. An interrelationship between the nutrient intake, including TDF, and the m...The daily intake of total dietary fiber (TDF) was evaluated from data of the National Nutrition Survey (NNS) in Japan for 41 years since 1947. An interrelationship between the nutrient intake, including TDF, and the mortality from colon cancer in Japanese people was calculated by a simple correlation coefficient and time-series correlation coeffcient.TDF intake per capita decreased rapidly from 27.4 g in 1947 to 15.8 g in 1963, and subsequently decreased by a lesser rate to 15.3 g in 1987. Fat intake increased rapidly from 18.0 g in 1950 to 56.6 g in 1987.The age-adjusted mortality from colon cancer shows a significant positive correlation with both the intakes of animal protein and of total fat, and the fat energy ratio. A time-series analysis indicates that the mortality from colon cancer was negatively correlated with TDF with a 15-27 year delay, the maximum correlation existing with a 23-year lag (r = -0.947). The TDF intake was less than 17.9 g in 1965. At the same time, the mortality from colon cancer increased rapidly. A fat/TDF ratio above 3.0 resulted in a rapid increase in colon cancer mortality.The non-adjusted mortality from colon cancer has much the same interrelationship with TDF and fat intake as the adjusted figures. It is suggested that the cause of the increased mortality from colon cancer in Japan is positively related to the increased intake of fat and protein. In addition, the decrease in TDF intake has accelerated the mortality of colon cancer after a delay of 23-24 years. The importance of fat/TDF as a nutritional criterion for the incidence of colon cancer needs to be better recognized展开更多
Using the software ANSYS-19.2/Explicit Dynamics,this study performedfinite-element modeling of the large-diameter steel pipeline cross-section for the Beineu-Bozoy-Shymkent gas pipeline with a non-through straight crac...Using the software ANSYS-19.2/Explicit Dynamics,this study performedfinite-element modeling of the large-diameter steel pipeline cross-section for the Beineu-Bozoy-Shymkent gas pipeline with a non-through straight crack,strengthened by steel wire wrapping.The effects of the thread tensile force of the steel winding in the form of single rings at the crack edges and the wires with different winding diameters and pitches were also studied.The results showed that the strengthening was preferably executed at a minimum value of the thread tensile force,which was 6.4%more effective than that at its maximum value.The analysis of the influence of the winding dia-meters showed that the equivalent stresses increased by 32%from the beginning of the crack growth until the wire broke.The increment in winding diameter decelerated the disclosure of the edge crack and reduced its length by 8.2%.The analysis of the influence of the winding pitch showed that decreasing the distance between the winding turns also led to a 33.6%reduction in the length of the straight crack and a 7.9%reduction in the maximum stres-ses on the strengthened pipeline cross-section.The analysis of the temperature effect on the pipeline material,within a range from-40℃to+50℃,resulted in a crack length change of up to 5.8%.As the temperature dropped,the crack length decreased.Within such a temperature range,the maximum stresses were observed along the cen-tral area of the crack,which were equal to 413 MPa at+50℃and 440 MPa at-40℃.The results also showed that the presence of the steel winding in the pipeline significantly reduced the length of crack propagation up to 8.4 times,depending on the temperature effect and design parameters of prestressing.This work integrated the existing methods for crack localization along steel gas pipelines.展开更多
The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmiss...The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmission electron microscopy,and X-ray diffraction analysis were conducted to characterize the progressive transformation-induced plasticity process and associated fracture initiation mechanisms.These findings were discussed with the local strain measurements via digital image correlation.The results indicated that Lüders band formation in the steel was limited to 1.5%strain,which was mainly due to the early-stage martensitic phase transformation of a very small amount of the less stable large-sized retained austenite(RA),which led to localized stress concentrations and strain hardening and further retardation of yielding.The small-sized RA exhibited high stability and progressively transformed into martensite and contributed to a stably extended Portevin-Le Chatelier effect.The volume fraction of RA gradually decreased from 26.8%to 8.2%prior to fracture.In the late deformation stage,fracture initiation primarily occurred at the austenite/martensite and ferrite/martensite interfaces and the ferrite phase.展开更多
In clinical studies,it is often that the medical treatments take a period of time before having an effect on patients and the delayed time may vary from person to person.Even though there exists a rich literature deve...In clinical studies,it is often that the medical treatments take a period of time before having an effect on patients and the delayed time may vary from person to person.Even though there exists a rich literature developing methods to estimate the time-lag period and treatment effects after lag time,most of these existing studies assume a fixed lag time.In this paper,we propose a hazard model incorporating a random treatment time-lag effect to describe the heterogeneous treatment effect among subjects.The EM algorithm is used to obtain the maximum likelihood estimator.We give the asymptotic properties of the proposed estimator and evaluate its performance via simulation studies.An application of the proposed method to real data is provided.展开更多
Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer...Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.展开更多
The flexoelectric effect refers to the electromechanical coupling between electric polarization and mechanical strain gradient.It universally exists in a variety of materials in any space group,such as liquid crystals...The flexoelectric effect refers to the electromechanical coupling between electric polarization and mechanical strain gradient.It universally exists in a variety of materials in any space group,such as liquid crystals,dielectrics,biological materials,and semiconductors.Because of its unique size effect,nanoscale flexoelectricity has shown novel phenomena and promising applications in electronics,optronics,mechatronics,and photovoltaics.In this review,we provide a succinct report on the discovery and development of the flexoelectric effect,focusing on flexoelectric materials and related applications.Finally,we discuss recent flexoelectric research progress and still‐unsolved problems.展开更多
This study explores the housing distribution effect of the Housing Provident Fund(HPF)system on households.Utilizing data from the China Household Finance Survey conducted in 2013,2015,2017,and 2019,this study empiric...This study explores the housing distribution effect of the Housing Provident Fund(HPF)system on households.Utilizing data from the China Household Finance Survey conducted in 2013,2015,2017,and 2019,this study empirically investigates this effect from two dimensions:the impact of HPF payments on household income and housing loan behavior,and the impact on the Gini coefficient of housing assets within the group.The results indicate that the HPF payment does not significantly impact household income levels.Instead,it increases their likelihood of obtaining housing loans,particularly for middle-income households.Additionally,for any group of families,the HPF payment decreased the housing Gini coefficient among households by approximately 0.11 units.This study may be the first to provide the most direct empirical evidence on the extent of HPF’s impact on housing inequality within a group.It also questions the inference in the literature that“HPF will aggravate housing inequality within the group.”Based on this study’s findings,we expect that housing inequality will continue to be alleviated with continued HPF implementation.In particular,this effect will be more significant if the credit support for lowincome families to purchase houses through the HPF can be further enhanced.展开更多
Agricultural intensification has led to an increase in monoculture and the use of chemical pesticides,resulting in a decline in biodiversity and a reduction in ecosystem services,particularly biological pest managemen...Agricultural intensification has led to an increase in monoculture and the use of chemical pesticides,resulting in a decline in biodiversity and a reduction in ecosystem services,particularly biological pest management.However,studies have shown that agroforestry can not only improve land productivity and biodiversity but also regulate some ecosystem services.This study reviews the impacts of physical and biological factors on herbivorous pests,parasites,and predatory natural enemies in fruit-crop agroforestry systems.Fruit-crop agroforestry systems provide high spatial heterogeneity by altering crop layouts,regulating the microclimate and soil quality,and offering food resources and shelter for natural enemies,thus promoting biological pest control.This enhances biological control and makes the agrocomplex system an effective tool for sustainable agriculture.Our research shows that volatile plant substances attract or repel pests and natural enemies based on the characteristics of the insects themselves.When scientifically designed,fruit-crop agroforestry systems provide high spatial heterogeneity and favorable microclimatic conditions,which enhance biological pest control and make the agroforestry system an effective tool for sustainable agriculture.Our research shows that fruit-crop agroforestry systems can provide richer food resources and habitat,enhancing biological pest control and improving pest management.展开更多
Fertilization or atmospheric deposition of nitrogen(N)and phosphorus(P)to terrestrial ecosystems can alter soil N(P)availability and the nature of nutrient limitation for plant growth.Changing the allocation of leaf P...Fertilization or atmospheric deposition of nitrogen(N)and phosphorus(P)to terrestrial ecosystems can alter soil N(P)availability and the nature of nutrient limitation for plant growth.Changing the allocation of leaf P fractions is potentially an adaptive strategy for plants to cope with soil N(P)availability and nutrient-limiting conditions.However,the impact of the interactions between imbalanced anthropogenic N and P inputs on the concentrations and allocation proportions of leaf P fractions in forest woody plants remains elusive.We conducted a metaanalysis of data about the concentrations and allocation proportions of leaf P fractions,specifically associated with individual and combined additions of N and P in evergreen forests,the dominant vegetation type in southern China where the primary productivity is usually considered limited by P.This assessment allowed us to quantitatively evaluate the effects of N and P additions alone and interactively on leaf P allocation and use strategies.Nitrogen addition(exacerbating P limitation)reduced the concentrations of leaf total P and different leaf P fractions.Nitrogen addition reduced the allocation to leaf metabolic P but increased the allocation to other fractions,while P addition showed opposite trends.The simultaneous additions of N and P showed an antagonistic(mutual suppression)effect on the concentrations of leaf P fractions,but an additive(summary)effect on the allocation proportions of leaf P fractions.These results highlight the importance of strategies of leaf P fraction allocation in forest plants under changes in environmental nutrient availability.Importantly,our study identified critical interactions associated with combined N and P inputs that affect leaf P fractions,thus aiding in predicting plant acclimation strategies in the context of intensifying and imbalanced anthropogenic nutrient inputs.展开更多
With the rapid development of artificial intelligence,magnetocaloric materials as well as other materials are being developed with increased efficiency and enhanced performance.However,most studies do not take phase t...With the rapid development of artificial intelligence,magnetocaloric materials as well as other materials are being developed with increased efficiency and enhanced performance.However,most studies do not take phase transitions into account,and as a result,the predictions are usually not accurate enough.In this context,we have established an explicable relationship between alloy compositions and phase transition by feature imputation.A facile machine learning is proposed to screen candidate NiMn-based Heusler alloys with desired magnetic entropy change and magnetic transition temperature with a high accuracy R^(2)≈0.98.As expected,the measured properties of prepared NiMn-based alloys,including phase transition type,magnetic entropy changes and transition temperature,are all in good agreement with the ML predictions.As well as being the first to demonstrate an explicable relationship between alloy compositions,phase transitions and magnetocaloric properties,our proposed ML model is highly predictive and interpretable,which can provide a strong theoretical foundation for identifying high-performance magnetocaloric materials in the future.展开更多
In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence ...In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.展开更多
Structural regulation of Pd-based electrocatalytic hydrodechlorination(EHDC)catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challe...Structural regulation of Pd-based electrocatalytic hydrodechlorination(EHDC)catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challenging.Herein,a support electron inductive effect of Pd-Mn/Ni foam catalyst was proposed via in-situ Mn doping to optimize the electronic structure of the Ni foam(NF),which can inductive regulation of Pd for improving the EHDC performance.The mass activity and current efficiency of Pd-Mn/NF catalyst are 2.91 and 1.34 times superior to that of Pd/NF with 2,4-dichlorophenol as model compound,respectively.The Mn-doped interlayer optimized the electronic structure of Pd by bringing the d-state closer to the Fermi level than Pd on the NF surface,which optimizied the binding of EHDC intermediates.Additionally,the Mn-doped interlayer acted as a promoter for generating H∗and accelerating the EHDC reaction.This work presents a simple and effective regulation strategy for constructing high-efficient cathode catalyst for the EHDC of chlorinated organic compounds.展开更多
Low-electrode capacitive deionization(FCDI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of waters.However,it still suffers from inefficient charge transfer...Low-electrode capacitive deionization(FCDI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of waters.However,it still suffers from inefficient charge transfer and ion transport kinetics due to weak turbulence and low electric intensity in flow electrodes,both restricted by the current collectors.Herein,a new tip-array current collector(designated as T-CC)was developed to replace the conventional planar current collectors,which intensifies both the charge transfer and ion transport significantly.The effects of tip arrays on flow and electric fields were studied by both computational simulations and electrochemical impedance spectroscopy,which revealed the reduction of ion transport barrier,charge transport barrier and internal resistance.With the voltage increased from 1.0 to 1.5 and 2.0 V,the T-CC-based FCDI system(T-FCDI)exhibited average salt removal rates(ASRR)of 0.18,0.50,and 0.89μmol cm^(-2) min^(-1),respectively,which are 1.82,2.65,and 2.48 folds higher than that of the conventional serpentine current collectors,and 1.48,1.67,and 1.49 folds higher than that of the planar current collectors.Meanwhile,with the solid content in flow electrodes increased from 1 to 5 wt%,the ASRR for T-FCDI increased from 0.29 to 0.50μmol cm^(-2) min^(-1),which are 1.70 and 1.67 folds higher than that of the planar current collectors.Additionally,a salt removal efficiency of 99.89%was achieved with T-FCDI and the charge efficiency remained above 95%after 24 h of operation,thus showing its superior long-term stability.展开更多
Objective The use of lasers has been an important part of urology in the treatment of stone and prostate disease.The thermal effects of lasers in lithotripsy have been a subject of debate over the years.The objective ...Objective The use of lasers has been an important part of urology in the treatment of stone and prostate disease.The thermal effects of lasers in lithotripsy have been a subject of debate over the years.The objective of this review was to assess the current state of knowledge available on the thermal effects of lasers in lithotripsy,as well as explore any new areas where studies are needed.Methods In August 2022,a keyword search on Google Scholar,PubMed,and Scopus for all papers containing the phrases“thermal effects”AND“laser”AND“lithotripsy”AND“urology”was done followed by citation jumping to other studies pertaining to the topic and 35 relevant papers were included in our study.The data from relevant papers were segregated into five groups according to the factor studied and type of study,and tables were created for a comparison of data.Results Temperature above the threshold of 43℃ was reached only when the power was>40 W and when there was adequate irrigation(at least 15–30 mL/min).Shorter lasing time divided by lithotripsy time or operator duty cycles less than 70%also resulted in a smaller temperature rise.Conclusion At least eight factors modify the thermal effects of lasers,and most importantly,the use of chilled irrigation at higher perfusion rates,lower power settings of<40 W,and with a shorter operator duty cycle will help to prevent thermal injuries from occurring.Stones impacted in the ureter or pelvi-ureteric junction further increase the probability of thermal injuries during laser firing.展开更多
As the main geomaterials for coral reefs oil or gas extraction and underground infrastructure construction,coral reef limestone demonstrates significantly distinct mechanical responses compared to terrigenous rocks.To...As the main geomaterials for coral reefs oil or gas extraction and underground infrastructure construction,coral reef limestone demonstrates significantly distinct mechanical responses compared to terrigenous rocks.To investigate the mechanical behaviour of coral reef limestone under the coupling impact of size and strain rate,the uniaxial compression tests were conducted on reef limestone samples with length-to-diameter(L/D)ratio ranging from 0.5 to 2.0 at strain rate ranging from 10^(−5)·s^(−1)to 10^(−2)·s^(−1).It is revealed that the uniaxial compressive strength(UCS)and residual compressive strength(RCS)of coral reef limestone exhibits a decreasing trend with L/D ratio increasing.The dynamic increase factor(DIF)of UCS is linearly correlated with the logarithm of strain rate,while increasing the L/D ratio further enhances the DIF.The elastic modulus increases with strain rate or L/D ratio increasing,whereas the Poisson’s ratio approximates to a constant value of 0.24.The failure strain increases with strain rate increasing or L/D ratio decreasing,while the increase in L/D ratio will inhibit the enhancing effect of the strain rate.The high porosity and low mineral strength are the primary factors contributing to a high RCS of 16.7%–64.9%of UCS,a lower brittleness index and multiple irregular fracture planes.The failure pattern of coral reef limestone transits from the shear-dominated to the splitting-dominated failure with strain rate increasing or L/D ratio decreasing,which is mainly governed by the constrained zones induced by end friction and the strain rate-dependent crack propagation.Moreover,a predictive formula incorporating coupling effect of size and strain rate for the UCS of reef limestone was established and verified to effectively capture the trend of UCS.展开更多
Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promi...Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.展开更多
Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapie...Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.展开更多
Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This s...Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.展开更多
基金Under the auspices of National Natural Science Foundation of China(No.42061020)Natural Science Foundation of Guangxi Zhuang Autonomous Region(No.2018JJA150135)+2 种基金Guangxi Key Research and Development Program(No.AA18118038)Science and Technology Department of Guangxi Zhuang Autonomous Region(No.2019AC20088)High Level Talent Introduction Project of Beibu Gulf University(No.2019KYQD28)。
文摘Scientific understanding of the trade-offs between services is crucial for the scientific management and protection of ecosystems and the formulation of resource management policies.This study integrated meteorological,land use,and soil data to assess the ecosystem services,namely,water yield(WY),soil erosion(SE),and carbon sinks(CS),in peak-cluster depression basins on the Sino-Vietnamese border in China during 2000-2020.It analyzed the trade-offs and synergistic relationships among the three ecosystem services and their time-lag effects and driving mechanisms with the help of pixel-by-pixel time-lag intercorrelation and geographical de-tector methods.Results show that:1)from 2000 to 2020,the key ecosystem service indicators in the peak-cluster depression basins on the Sino-Vietnamese border in China demonstrated a significant and synergistic trend of positive change.The WY increased at a rate of 11.99 mm/yr,CS increased at a rate of 2.44 g C/(m^(2)∙yr),and SE decreased at a rate of 0.06 t/(ha∙yr).2)Most areas showed a synergistic relationship across the three ecosystem services,and the areas with a trade-off relationship were mostly concentrated in Baise City and the southwest of Chongzuo City,Guangxi.3)The time-lag effect between SE and WY was mostly concentrated in 0 yr,that between SE and CS was mostly concentrated in 5 yr,and that between CS and WY was mostly concentrated in 1 yr.4)Population density was the controlling factor between SE and WY.Vegetation coverage factor is the main controlling factor between SE and CS.The lithologic factor is the main controlling factor between CS and WY.Studying the trade-off relationship of ecosystem services at spatial and tem-poral scales on the Sino-Vietnamese border in China karst areas can provide a basis for regional ecological construction and develop-ment strategies,and it is conducive to meeting regional interest needs,maximizing comprehensive benefits,balancing the ecological en-vironment,and achieving regional sustainable development.
基金National Natural Science Foundation of China,No.42161058The State Key Laboratory of Cryospheric Science,No.SKLCS-ZZ-2022The West Light Foundation of the Chinese Academy of Sciences。
文摘Most terrestrial models synchronously calculate net primary productivity(NPP)using the input climate variable,without the consideration of time-lag effects,which may increase the uncertainty of NPP simulation.Based on Normalized Difference Vegetation Index(NDVI)and climate data,we used the time lag cross-correlation method to investigate the time-lag effects of temperature,precipitation,and solar radiation in different seasons on NDVI values.Then,we selected the Carnegie-Ames-Stanford approach(CASA)model to estimate the NPP of China from 2002 to 2017.The results showed that the response of vegetation growth to climate factors had an obvious lag effect,with the longest time lag in solar radiation and the shortest time lag in temperature.The time lag of vegetation to the climate variable showed great tempo-spatial heterogeneities among vegetation types,climate types,and vegetation growth periods.Based on the validation using eddy covariance data,the results showed that the simulation accuracy of the CASA model considering the time-lag effects was effectively improved.By considering the time-lag effects,the average total amount of NPP modeled by CASA during 2001-2017 in China was 3.977 PgC a^(−1),which is 11.37%higher than that of the original model.This study highlights the importance of considering the time lag for the simulation of vegetation growth,and provides a useful tool for the improvement of the vegetation productivity model.
文摘The daily intake of total dietary fiber (TDF) was evaluated from data of the National Nutrition Survey (NNS) in Japan for 41 years since 1947. An interrelationship between the nutrient intake, including TDF, and the mortality from colon cancer in Japanese people was calculated by a simple correlation coefficient and time-series correlation coeffcient.TDF intake per capita decreased rapidly from 27.4 g in 1947 to 15.8 g in 1963, and subsequently decreased by a lesser rate to 15.3 g in 1987. Fat intake increased rapidly from 18.0 g in 1950 to 56.6 g in 1987.The age-adjusted mortality from colon cancer shows a significant positive correlation with both the intakes of animal protein and of total fat, and the fat energy ratio. A time-series analysis indicates that the mortality from colon cancer was negatively correlated with TDF with a 15-27 year delay, the maximum correlation existing with a 23-year lag (r = -0.947). The TDF intake was less than 17.9 g in 1965. At the same time, the mortality from colon cancer increased rapidly. A fat/TDF ratio above 3.0 resulted in a rapid increase in colon cancer mortality.The non-adjusted mortality from colon cancer has much the same interrelationship with TDF and fat intake as the adjusted figures. It is suggested that the cause of the increased mortality from colon cancer in Japan is positively related to the increased intake of fat and protein. In addition, the decrease in TDF intake has accelerated the mortality of colon cancer after a delay of 23-24 years. The importance of fat/TDF as a nutritional criterion for the incidence of colon cancer needs to be better recognized
基金funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan(Grant No.AP19680589).
文摘Using the software ANSYS-19.2/Explicit Dynamics,this study performedfinite-element modeling of the large-diameter steel pipeline cross-section for the Beineu-Bozoy-Shymkent gas pipeline with a non-through straight crack,strengthened by steel wire wrapping.The effects of the thread tensile force of the steel winding in the form of single rings at the crack edges and the wires with different winding diameters and pitches were also studied.The results showed that the strengthening was preferably executed at a minimum value of the thread tensile force,which was 6.4%more effective than that at its maximum value.The analysis of the influence of the winding dia-meters showed that the equivalent stresses increased by 32%from the beginning of the crack growth until the wire broke.The increment in winding diameter decelerated the disclosure of the edge crack and reduced its length by 8.2%.The analysis of the influence of the winding pitch showed that decreasing the distance between the winding turns also led to a 33.6%reduction in the length of the straight crack and a 7.9%reduction in the maximum stres-ses on the strengthened pipeline cross-section.The analysis of the temperature effect on the pipeline material,within a range from-40℃to+50℃,resulted in a crack length change of up to 5.8%.As the temperature dropped,the crack length decreased.Within such a temperature range,the maximum stresses were observed along the cen-tral area of the crack,which were equal to 413 MPa at+50℃and 440 MPa at-40℃.The results also showed that the presence of the steel winding in the pipeline significantly reduced the length of crack propagation up to 8.4 times,depending on the temperature effect and design parameters of prestressing.This work integrated the existing methods for crack localization along steel gas pipelines.
基金supported by the National Key R&D Program of China(No.2017YFB0304402)。
文摘The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile testing.In-situ observations under scanning electron microscopy,transmission electron microscopy,and X-ray diffraction analysis were conducted to characterize the progressive transformation-induced plasticity process and associated fracture initiation mechanisms.These findings were discussed with the local strain measurements via digital image correlation.The results indicated that Lüders band formation in the steel was limited to 1.5%strain,which was mainly due to the early-stage martensitic phase transformation of a very small amount of the less stable large-sized retained austenite(RA),which led to localized stress concentrations and strain hardening and further retardation of yielding.The small-sized RA exhibited high stability and progressively transformed into martensite and contributed to a stably extended Portevin-Le Chatelier effect.The volume fraction of RA gradually decreased from 26.8%to 8.2%prior to fracture.In the late deformation stage,fracture initiation primarily occurred at the austenite/martensite and ferrite/martensite interfaces and the ferrite phase.
基金Supported by the National Natural Science Foundation of China(Grant No.11971362)。
文摘In clinical studies,it is often that the medical treatments take a period of time before having an effect on patients and the delayed time may vary from person to person.Even though there exists a rich literature developing methods to estimate the time-lag period and treatment effects after lag time,most of these existing studies assume a fixed lag time.In this paper,we propose a hazard model incorporating a random treatment time-lag effect to describe the heterogeneous treatment effect among subjects.The EM algorithm is used to obtain the maximum likelihood estimator.We give the asymptotic properties of the proposed estimator and evaluate its performance via simulation studies.An application of the proposed method to real data is provided.
基金the financial support from Henan Province Natural Science Foundation(No.252300420583)Henan Provincial Science and Technology Research Project(Nos.242102310455,242102310473,242102310517)the Key Project of Science and Technology Research funded by the Henan Provincial Department of Education(No.24A350002)。
文摘Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.
基金support of the National Natural Science Foundation of China(Grant Nos.52192611,51872031,61904013,and 62405157)China Postdoctoral Science Foundation(Nos.2023M741890 and GZC20231215)the Fundamental Research Funds for the Central Universities.
文摘The flexoelectric effect refers to the electromechanical coupling between electric polarization and mechanical strain gradient.It universally exists in a variety of materials in any space group,such as liquid crystals,dielectrics,biological materials,and semiconductors.Because of its unique size effect,nanoscale flexoelectricity has shown novel phenomena and promising applications in electronics,optronics,mechatronics,and photovoltaics.In this review,we provide a succinct report on the discovery and development of the flexoelectric effect,focusing on flexoelectric materials and related applications.Finally,we discuss recent flexoelectric research progress and still‐unsolved problems.
基金funded by the Humanities and Social Sciences Research Project of the Ministry of Education of China(Project No.23XJC790007).
文摘This study explores the housing distribution effect of the Housing Provident Fund(HPF)system on households.Utilizing data from the China Household Finance Survey conducted in 2013,2015,2017,and 2019,this study empirically investigates this effect from two dimensions:the impact of HPF payments on household income and housing loan behavior,and the impact on the Gini coefficient of housing assets within the group.The results indicate that the HPF payment does not significantly impact household income levels.Instead,it increases their likelihood of obtaining housing loans,particularly for middle-income households.Additionally,for any group of families,the HPF payment decreased the housing Gini coefficient among households by approximately 0.11 units.This study may be the first to provide the most direct empirical evidence on the extent of HPF’s impact on housing inequality within a group.It also questions the inference in the literature that“HPF will aggravate housing inequality within the group.”Based on this study’s findings,we expect that housing inequality will continue to be alleviated with continued HPF implementation.In particular,this effect will be more significant if the credit support for lowincome families to purchase houses through the HPF can be further enhanced.
文摘Agricultural intensification has led to an increase in monoculture and the use of chemical pesticides,resulting in a decline in biodiversity and a reduction in ecosystem services,particularly biological pest management.However,studies have shown that agroforestry can not only improve land productivity and biodiversity but also regulate some ecosystem services.This study reviews the impacts of physical and biological factors on herbivorous pests,parasites,and predatory natural enemies in fruit-crop agroforestry systems.Fruit-crop agroforestry systems provide high spatial heterogeneity by altering crop layouts,regulating the microclimate and soil quality,and offering food resources and shelter for natural enemies,thus promoting biological pest control.This enhances biological control and makes the agrocomplex system an effective tool for sustainable agriculture.Our research shows that volatile plant substances attract or repel pests and natural enemies based on the characteristics of the insects themselves.When scientifically designed,fruit-crop agroforestry systems provide high spatial heterogeneity and favorable microclimatic conditions,which enhance biological pest control and make the agroforestry system an effective tool for sustainable agriculture.Our research shows that fruit-crop agroforestry systems can provide richer food resources and habitat,enhancing biological pest control and improving pest management.
基金supported by the National Natural Science Foundation of China(No.41473068)supported by China Postdoctoral Science Foundation(No.2022M722667)。
文摘Fertilization or atmospheric deposition of nitrogen(N)and phosphorus(P)to terrestrial ecosystems can alter soil N(P)availability and the nature of nutrient limitation for plant growth.Changing the allocation of leaf P fractions is potentially an adaptive strategy for plants to cope with soil N(P)availability and nutrient-limiting conditions.However,the impact of the interactions between imbalanced anthropogenic N and P inputs on the concentrations and allocation proportions of leaf P fractions in forest woody plants remains elusive.We conducted a metaanalysis of data about the concentrations and allocation proportions of leaf P fractions,specifically associated with individual and combined additions of N and P in evergreen forests,the dominant vegetation type in southern China where the primary productivity is usually considered limited by P.This assessment allowed us to quantitatively evaluate the effects of N and P additions alone and interactively on leaf P allocation and use strategies.Nitrogen addition(exacerbating P limitation)reduced the concentrations of leaf total P and different leaf P fractions.Nitrogen addition reduced the allocation to leaf metabolic P but increased the allocation to other fractions,while P addition showed opposite trends.The simultaneous additions of N and P showed an antagonistic(mutual suppression)effect on the concentrations of leaf P fractions,but an additive(summary)effect on the allocation proportions of leaf P fractions.These results highlight the importance of strategies of leaf P fraction allocation in forest plants under changes in environmental nutrient availability.Importantly,our study identified critical interactions associated with combined N and P inputs that affect leaf P fractions,thus aiding in predicting plant acclimation strategies in the context of intensifying and imbalanced anthropogenic nutrient inputs.
基金supported by the National Key R&D Program of China(No.2022YFE0109500)the National Natural Science Foundation of China(Nos.52071255,52301250,52171190 and 12304027)+2 种基金the Key R&D Project of Shaanxi Province(No.2022GXLH-01-07)the Fundamental Research Funds for the Central Universities(China)the World-Class Universities(Disciplines)and the Characteristic Development Guidance Funds for the Central Universities.
文摘With the rapid development of artificial intelligence,magnetocaloric materials as well as other materials are being developed with increased efficiency and enhanced performance.However,most studies do not take phase transitions into account,and as a result,the predictions are usually not accurate enough.In this context,we have established an explicable relationship between alloy compositions and phase transition by feature imputation.A facile machine learning is proposed to screen candidate NiMn-based Heusler alloys with desired magnetic entropy change and magnetic transition temperature with a high accuracy R^(2)≈0.98.As expected,the measured properties of prepared NiMn-based alloys,including phase transition type,magnetic entropy changes and transition temperature,are all in good agreement with the ML predictions.As well as being the first to demonstrate an explicable relationship between alloy compositions,phase transitions and magnetocaloric properties,our proposed ML model is highly predictive and interpretable,which can provide a strong theoretical foundation for identifying high-performance magnetocaloric materials in the future.
文摘In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.
基金supported by the National Natural Science Foundation of China(Nos.22178388 and 22108306)Taishan Scholars Program of Shandong Province(No.tsqn201909065)Chongqing Science and Technology Bureau(No.cstc2019jscx-gksb X0032).
文摘Structural regulation of Pd-based electrocatalytic hydrodechlorination(EHDC)catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challenging.Herein,a support electron inductive effect of Pd-Mn/Ni foam catalyst was proposed via in-situ Mn doping to optimize the electronic structure of the Ni foam(NF),which can inductive regulation of Pd for improving the EHDC performance.The mass activity and current efficiency of Pd-Mn/NF catalyst are 2.91 and 1.34 times superior to that of Pd/NF with 2,4-dichlorophenol as model compound,respectively.The Mn-doped interlayer optimized the electronic structure of Pd by bringing the d-state closer to the Fermi level than Pd on the NF surface,which optimizied the binding of EHDC intermediates.Additionally,the Mn-doped interlayer acted as a promoter for generating H∗and accelerating the EHDC reaction.This work presents a simple and effective regulation strategy for constructing high-efficient cathode catalyst for the EHDC of chlorinated organic compounds.
基金supported by the Shenzhen Science and Technology Program(JCYJ20230808105111022,JCYJ20220818095806013)Natural Science Foundation of Guangdong(2023A1515012267)+1 种基金the National Natural Science Foundation of China(22178223)the Royal Society/NSFC cost share program(IEC\NSFC\223372).
文摘Low-electrode capacitive deionization(FCDI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of waters.However,it still suffers from inefficient charge transfer and ion transport kinetics due to weak turbulence and low electric intensity in flow electrodes,both restricted by the current collectors.Herein,a new tip-array current collector(designated as T-CC)was developed to replace the conventional planar current collectors,which intensifies both the charge transfer and ion transport significantly.The effects of tip arrays on flow and electric fields were studied by both computational simulations and electrochemical impedance spectroscopy,which revealed the reduction of ion transport barrier,charge transport barrier and internal resistance.With the voltage increased from 1.0 to 1.5 and 2.0 V,the T-CC-based FCDI system(T-FCDI)exhibited average salt removal rates(ASRR)of 0.18,0.50,and 0.89μmol cm^(-2) min^(-1),respectively,which are 1.82,2.65,and 2.48 folds higher than that of the conventional serpentine current collectors,and 1.48,1.67,and 1.49 folds higher than that of the planar current collectors.Meanwhile,with the solid content in flow electrodes increased from 1 to 5 wt%,the ASRR for T-FCDI increased from 0.29 to 0.50μmol cm^(-2) min^(-1),which are 1.70 and 1.67 folds higher than that of the planar current collectors.Additionally,a salt removal efficiency of 99.89%was achieved with T-FCDI and the charge efficiency remained above 95%after 24 h of operation,thus showing its superior long-term stability.
文摘Objective The use of lasers has been an important part of urology in the treatment of stone and prostate disease.The thermal effects of lasers in lithotripsy have been a subject of debate over the years.The objective of this review was to assess the current state of knowledge available on the thermal effects of lasers in lithotripsy,as well as explore any new areas where studies are needed.Methods In August 2022,a keyword search on Google Scholar,PubMed,and Scopus for all papers containing the phrases“thermal effects”AND“laser”AND“lithotripsy”AND“urology”was done followed by citation jumping to other studies pertaining to the topic and 35 relevant papers were included in our study.The data from relevant papers were segregated into five groups according to the factor studied and type of study,and tables were created for a comparison of data.Results Temperature above the threshold of 43℃ was reached only when the power was>40 W and when there was adequate irrigation(at least 15–30 mL/min).Shorter lasing time divided by lithotripsy time or operator duty cycles less than 70%also resulted in a smaller temperature rise.Conclusion At least eight factors modify the thermal effects of lasers,and most importantly,the use of chilled irrigation at higher perfusion rates,lower power settings of<40 W,and with a shorter operator duty cycle will help to prevent thermal injuries from occurring.Stones impacted in the ureter or pelvi-ureteric junction further increase the probability of thermal injuries during laser firing.
基金supported by the National Natural Science Foundation of China(Nos.52222110,52401354,and 52301353).
文摘As the main geomaterials for coral reefs oil or gas extraction and underground infrastructure construction,coral reef limestone demonstrates significantly distinct mechanical responses compared to terrigenous rocks.To investigate the mechanical behaviour of coral reef limestone under the coupling impact of size and strain rate,the uniaxial compression tests were conducted on reef limestone samples with length-to-diameter(L/D)ratio ranging from 0.5 to 2.0 at strain rate ranging from 10^(−5)·s^(−1)to 10^(−2)·s^(−1).It is revealed that the uniaxial compressive strength(UCS)and residual compressive strength(RCS)of coral reef limestone exhibits a decreasing trend with L/D ratio increasing.The dynamic increase factor(DIF)of UCS is linearly correlated with the logarithm of strain rate,while increasing the L/D ratio further enhances the DIF.The elastic modulus increases with strain rate or L/D ratio increasing,whereas the Poisson’s ratio approximates to a constant value of 0.24.The failure strain increases with strain rate increasing or L/D ratio decreasing,while the increase in L/D ratio will inhibit the enhancing effect of the strain rate.The high porosity and low mineral strength are the primary factors contributing to a high RCS of 16.7%–64.9%of UCS,a lower brittleness index and multiple irregular fracture planes.The failure pattern of coral reef limestone transits from the shear-dominated to the splitting-dominated failure with strain rate increasing or L/D ratio decreasing,which is mainly governed by the constrained zones induced by end friction and the strain rate-dependent crack propagation.Moreover,a predictive formula incorporating coupling effect of size and strain rate for the UCS of reef limestone was established and verified to effectively capture the trend of UCS.
基金Supported by the National Natural Science Foundation of China,No.82072537the General Project of Hunan Natural Science Foundation,No.2022JJ30412 and No.2021JJ30464.
文摘Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.
文摘Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.
基金supported by the National Natural Science Foundation of China(Nos.82274211 and 82474190)the Natural Science Foundation of Tianjin(Nos.24JCZDJC00120 and 24PTLYHZ00280)Liaoning Provincial Department of Education Basic Research Projects for Higher Education Institutions(No.LJ212510163021)。
文摘Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
