Golgi apparatus(GA)-associated secretome runs through the endomembrane system and is critical for inter-and intracellular communication networks.However,achieving in situ dissection of the GA-associated secretome rema...Golgi apparatus(GA)-associated secretome runs through the endomembrane system and is critical for inter-and intracellular communication networks.However,achieving in situ dissection of the GA-associated secretome remains challenging owing to the scarcity of specific labeling methods.This work develops an aggregation-induced emission(AIE)luminogen-mediated photocatalytic proximity labeling strategy that allows profiling of the GA-associated secretome with high spatiotemporal precision.Leveraging an AIE luminogen-derived GA-targeting photocatalyst,this strategy achieves efficient labeling of proteins in minutes within the Golgi lumen upon light activation,which enables spatiotemporally resolved modification of histidine and tyrosine residues.We succeed in profiling secretome in both living HeLa cells and hard-to-transfect macrophage HMC3 cells,and a significant subset of GA-associated secretome with 80%specificity is determined,linking the distinct GA-associated secretory profiles to cellular characteristics.The method is further applied to proteome mapping of brain and bone metastatic lung cancer cells,which reveals the underlying roles the GA-associated secretome plays in extracellular matrix organization during metastasis.This work delivers a robust tool to break the dilemma of chemical labeling of GA-associated secretome in living cells,and provides mechanistic insights into secretion regulation at the subcellular level.展开更多
核型分析作为产前诊断常规项目应用于遗传学诊断和遗传咨询。染色体多态性在核型分析中很常见,但因缺乏以图示为参照的多态性判断标准,使各实验室对同一染色体变异是否应判断为多态性以及用什么符号表达多态性存在差异,从而影响核型分...核型分析作为产前诊断常规项目应用于遗传学诊断和遗传咨询。染色体多态性在核型分析中很常见,但因缺乏以图示为参照的多态性判断标准,使各实验室对同一染色体变异是否应判断为多态性以及用什么符号表达多态性存在差异,从而影响核型分析报告的互认及多态性的临床解读。本共识通过采集已确诊的各种多态性核型图,研究其在不同显带技术中的形态特征,比较各种多态性的G带、C带和N带的特征异同,确认多态性G带特征,并参照《人类细胞基因组学国际命名体系(ISCN 2024)》(An International System for Human Cytogenomic Nomenclature,ISCN 2024)进行多态性归类,提出判断标准、鉴别流程、知情告知和临床解读模式,以规范多态性判别,促进核型分析报告互认,确保遗传咨询结果一致,解决本行业长期困扰的多态性判断标准缺乏和同一多态性被不同解读的遗传咨询问题。展开更多
With the increasing integration of large-scale distributed energy resources into the grid,traditional distribution network optimization and dispatch methods struggle to address the challenges posed by both generation ...With the increasing integration of large-scale distributed energy resources into the grid,traditional distribution network optimization and dispatch methods struggle to address the challenges posed by both generation and load.Accounting for these issues,this paper proposes a multi-timescale coordinated optimization dispatch method for distribution networks.First,the probability box theory was employed to determine the uncertainty intervals of generation and load forecasts,based on which,the requirements for flexibility dispatch and capacity constraints of the grid were calculated and analyzed.Subsequently,a multi-timescale optimization framework was constructed,incorporating the generation and load forecast uncertainties.This framework included optimization models for dayahead scheduling,intra-day optimization,and real-time adjustments,aiming to meet flexibility needs across different timescales and improve the economic efficiency of the grid.Furthermore,an improved soft actor-critic algorithm was introduced to enhance the uncertainty exploration capability.Utilizing a centralized training and decentralized execution framework,a multi-agent SAC network model was developed to improve the decision-making efficiency of the agents.Finally,the effectiveness and superiority of the proposed method were validated using a modified IEEE-33 bus test system.展开更多
Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in million...Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in millions of fatalities each year.Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication,their ability to reduce hepatitis B surface antigen(HBsAg)levels in plasma remains limited.The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions,rendering long-term administration challenging.Therefore,current drug development efforts for chronic hepatitis B aim to achieve a functional cure,which is defined as HBsAg serological clearance and sustained suppression of HBV DNA.This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors,monoclonal antibodies,RNA interferences,and other agents that directly target the virus.Furthermore,we discuss the development of immunomodulatory therapies,including TLR-7/8 agonists,immune checkpoint inhibitors,and therapeutic vaccines.In the end,we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.展开更多
Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potentia...Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.展开更多
The Maoping lead–zinc mining area is a significant metal mine site in northeastern Yunnan.In this study,both hydraulic fracturing in situ stress testing and ultrasonic imaging logging were first carried out in the mi...The Maoping lead–zinc mining area is a significant metal mine site in northeastern Yunnan.In this study,both hydraulic fracturing in situ stress testing and ultrasonic imaging logging were first carried out in the mining area.Second,930 focal mechanism solutions and 231 sets of stress data near the mining area were collected.Then,the variations in the type of in situ stress field,the magnitude of in situ stress,the direction of horizontal principal stress,and the ratio of lateral pressure were analyzed to characterize the distribution of the in situ stress field.On this basis,a new method using borehole breakouts and drilling-induced fractures was proposed to determine the stress direction.Finally,the evolution of the mechanical properties of dolomite with burial depth was analyzed and the influence of rock mechanical properties on the distributions of the in situ stress field was explored.The results show that the in situ stress in the mining area isσ_(H)>σ_(V)>σ_(h),indicating a strike–slip stress state.The in situ stress is high in magnitude,and its value increases with burial depth.The maximum and minimum horizontal lateral stress coefficients are stabilized at approximately 1.22 and 0.73,respectively.The direction of the maximum horizontal principal stress is NW,mainly ranging from N58.44°W to N59.70°W.The stress field inferred from the focal mechanism solution is in good agreement with the test results.The proportion of structural planes with dip angles between 30°and 75°exceeds 80%,and the dip direction of the structural planes is mainly NW to NWW.The line density of structural planes shows high density in shallow areas and low density in deep areas.More energy tends to be accumulated in rocks with higher elastic modulus and strength,leading to higher in situ stress levels.These findings are of significant reference for mine tunnel layout,support design optimization,and disaster prevention.展开更多
Purpose Lateral ankle sprains(LAS)are associated with corticospinal pathway deficits.Existing evidence is primarily based on cross-sectional investigations and noncausal speculations.This study aims to determine wheth...Purpose Lateral ankle sprains(LAS)are associated with corticospinal pathway deficits.Existing evidence is primarily based on cross-sectional investigations and noncausal speculations.This study aims to determine whether maladaptive corticospinal pathway alterations occur pre-and postligament transection in LAS mouse models.Additionally,this study explores whether the alterations are more pronounced in adolescent mice than adults.Methods Twenty-four 8-week-old adolescent and twenty-four 24-week-old adult mice were randomly assigned to lateral ankle ligament transection or sham surgery.Diffusion-weighted imaging of the corticospinal pathway was performed presurgery and 8 weeks postsurgery.Fractional anisotropy(FA)values,reflecting fiber integrity within the corticospinal subregions of the medulla,pons,midbrain,and cerebrum,were extracted.Results Overall,41 mice completed repeated image acquisition.Before surgery,no significant group effects on FA within the four corticospinal subregions were detected in either adolescent or adult mice.Two months after surgery,the adolescent cohort displayed a significant reduction in FA in the medulla subregion following ankle ligament transection(β-baseline-adjusted=-0.083,95%CI,-0.145 to-0.021,p-corrected=0.048).Conversely,no significant effects of ankle ligament transection on corticospinal FA were observed in the adult cohort.Conclusion The maladaptive alterations in the corticospinal tract could be observed in the adolescent LAS mouse model,characterized by reduced fiber integrity in the medulla subregion.While these results are derived from an animal model,they provide a foundation for future investigations into the mechanisms underlying neurological deficits following musculoskeletal injuries.展开更多
Older adults are at an increased risk of developing knee osteoarthritis.High internal knee abduction moment during daily activities may elevate the risk of knee osteoarthritis.Incline walking exercise has been found t...Older adults are at an increased risk of developing knee osteoarthritis.High internal knee abduction moment during daily activities may elevate the risk of knee osteoarthritis.Incline walking exercise has been found to decrease knee abduction moment in healthy young adults.However,it is unknown if this occurs in healthy older adults.The purpose of this study was to quantify the internal knee abduction moment at different treadmill grades to determine if incline walking could reduce the knee abduction moment in healthy older adults.Twelve healthy older adult males walked on a treadmill at five incline grades(0%,5%,10%,15%,and 20%)at 1.34 m·s^(-1).The primary outcome variable was the internal knee abduction moment.A one-way repeated measures multivariate analysis of variance was performed to determine differences in the dependent variables among incline gradients.Peak knee abduction moment significantly decreased from level walking at all gradients in 10% increments(0%-10%,p<0.001;5%-15%,p<0.002;and 10%-20%,p=0.04).A reduction in knee abduction moment during incline walking could result in decreased knee joint loading on the medial knee compartment.For older adults,who are looking to exercise to improve their health,incline walking may be beneficial to promote lower body strength and cardiovascular ability without inflicting further harm to the aging knee joints.However,because the frontal plane knee joint was of primary interest in this study,further research is needed to determine the effects of incline walking on other joints and in other planes of motion.展开更多
This article explores the role of distributed energy resources such as efficient solar cells that drive carbon neutrality within the solar energy. For example, the perovskite solar cells offer high efficiency and pote...This article explores the role of distributed energy resources such as efficient solar cells that drive carbon neutrality within the solar energy. For example, the perovskite solar cells offer high efficiency and potential for low-cost production. A novel theoretical model is discovered in distributed energy resources for power emissions and cost. The smart carbon neutrality approaches are analyzed in both theory and experiments. The advantages, current challenges, and future prospects of the related solutions are discussed methodically. By addressing stability and scalability issues, these approaches can contribute significantly to reducing carbon emissions and promoting sustainable energy solutions.展开更多
The detection of gravitational waves by the LIGO-Virgo-KAGRA collaboration has ushered in a new era of observational astronomy,emphasizing the need for rapid and detailed parameter estimation and population-level anal...The detection of gravitational waves by the LIGO-Virgo-KAGRA collaboration has ushered in a new era of observational astronomy,emphasizing the need for rapid and detailed parameter estimation and population-level analyses.Traditional Bayesian inference methods,particularly Markov chain Monte Carlo,face significant computational challenges when dealing with the high-dimensional parameter spaces and complex noise characteristics inherent in gravitational wave data.This review examines the emerging role of simulation-based inference methods in gravitational wave astronomy,with a focus on approaches that leverage machine-learning techniques such as normalizing flows and neural posterior estimation.We provide a comprehensive overview of the theoretical foundations underlying various simulation-based inference methods,including neural posterior estimation,neural ratio estimation,neural likelihood estimation,flow matching,and consistency models.We explore the applications of these methods across diverse gravitational wave data processing scenarios,from single-source parameter estimation and overlapping signal analysis to testing general relativity and conducting population studies.Although these techniques demonstrate speed improvements over traditional methods in controlled studies,their model-dependent nature and sensitivity to prior assumptions are barriers to their widespread adoption.Their accuracy,which is similar to that of conventional methods,requires further validation across broader parameter spaces and noise conditions.展开更多
Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although th...Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.展开更多
This work investigated the distribution and speciation of Cd,Cu,Pb,Fe and Mn in the shallow sediments of Jinzhou Bay,Northeast China,which has been heavily contaminated by nonferrous smelting activities.The concentrat...This work investigated the distribution and speciation of Cd,Cu,Pb,Fe and Mn in the shallow sediments of Jinzhou Bay,Northeast China,which has been heavily contaminated by nonferrous smelting activities.The concentrations of Cd,Cu and Pb in sediments were found to be 100,13 and 7 times,respectively,being higher than the national guideline(GB 18668-2002).Sequential extraction test showed that 39%-61%of Cd were exchangeable fractions,indicating that Cd in the sediments posed a high risk to local environments.While Cu and Pb were at moderate risk levels.According to the relationships between percentage of metal speciation and total metal concentration,it was concluded that the distributions of Cd,Cu and Pb in some geochemical fractions were dynamic in the process of pollutants migration and the stability of metals in sediments of Jinzhou Bay decreased in the order of Pb〉Cu〉Cd.展开更多
Purpose:Ankle proprioception deficits have been widely reported in patients with chronic ankle instability(CAI),but their central neuropathological mechanisms have not been fully discussed.So,we aimed to figure out wh...Purpose:Ankle proprioception deficits have been widely reported in patients with chronic ankle instability(CAI),but their central neuropathological mechanisms have not been fully discussed.So,we aimed to figure out whether the structural and functional features of the cerebellar vermis differed between patients with CAI and healthy controls,and are associated with proprioception deficits in patients.Methods:Twenty-two patients and 25 control individuals were enrolled in a cross-sectional investigation.All participants underwent structural and resting-state functional magnetic resonance imaging scanning to calculate voxel-based morphometry(VBM)and fractional amplitude of low-frequency fluctuation(fALFF)of the vermis.Between-group comparisons of the ankle instability-related subregions of the vermis were performed.Correlation analyses were performed between the outcomes of the surviving subregions and the proprioceptive scores of the ankle inversion discrimination apparatus for landing test.Results:The subregion of vermis Ⅳ/Ⅴ survived the multiple comparison correction to reveal a lower VBM value in patients than in healthy controls(Cohen's d=-0.968).The patients also showed significantly higher fALFF(Cohen's d=0.666)in this subregion.After controlling the demographic features,the proprioceptive scores were significantly correlated with VBM(r=0.622)and fALFF values(r=-0.512)in the group of patients.Conclusions:Patients with CAI have lower gray matter volume and higher activity intensity in the cerebellar vermis than healthy control.The more severe proprioception deficits were significantly associated with the vermal volume and activity,which might be able to facilitate future diagnoses and treatments for CAI.展开更多
Aim： To explore the effect of androgen receptor （AR） on the expression of the cell cycle-related genes, such as CDKNIA and BTG1, in prostate cancer cell line LNCaP. Methods： After AR antagonist flutamide treatment...Aim： To explore the effect of androgen receptor （AR） on the expression of the cell cycle-related genes, such as CDKNIA and BTG1, in prostate cancer cell line LNCaP. Methods： After AR antagonist flutamide treatment and confirmation of its effect by phase contrast microscope and flow cytometry, the differential expression of the cell cycle-related genes was analyzed by a cDNA microarray. The flutamide treated cells were set as the experimental group and the LNCaP cells as the control. We labeled cDNA probes of the experimental group and control group with Cy5 and Cy3 dyes, respectively, through reverse transcription. Then we hybridized the cDNA probes with cDNA microarrays, which contained 8 126 unique human cDNA sequences and the chip was scanned to get the fluorescent values of Cy5 and Cy3 on each spot. After primary analysis, reverse transcription polymerase chain reaction （RT- PCR） tests were carried out to confirm the results of the chips. Results：After AR antagonist flutamide treatment, three hundred and twenty-six genes （3.93 %） expressed differentially, 97 down-regulated and 219 up-regulated. Among them, eight up-regulated genes might be cell cycle-related, namely CDCIO, NRAS, BTG1, Wee1, CLK3, DKFZP564A122, CDKNIA and BTG2. The CDKNIA and BTG1 gene mRNA expression was confirmed to be higher in the experimental group by RT-PCR, while p53 mRNA expression had no significant changes. Conclusion： Flutamide treatment might up-regulate CDKN1A and BTG1 expression in prostate cancer cells. The protein expressions of CDKN1A and BTG1 play an important role in inhibiting the proliferation of cancer cells. CDKN1A has a great impact on the cell cycle of prostate cancer cells and may play a role in the cancer cells in a p53-independent pathway. The prostate cancer cells might affect the cell cycle-related genes by activating AR and thus break the cell cycle control.展开更多
Syringa species not only have good ornamental properties but also play an important role in the landscaping and environmental purification of cities.To investigate the chilling stress resistance of Syringa oblata Lind...Syringa species not only have good ornamental properties but also play an important role in the landscaping and environmental purification of cities.To investigate the chilling stress resistance of Syringa oblata Lindl.and Syringa reticulata var.mandshurica and provide theoretical grounds for the practical cultivation of Syringa species,in vitro leaves were used to study photosynthetic gas exchange parameters and chlorophyll fluorescence parameters.After nine hours of chilling,decreasing rates of net photosynthesis,stomatal conductance,and transpiration in S.reticulata var.mandshurica leaves were significantly greater than that of the S.oblata,while intercellular CO2 concentrations in S.oblata leaves were higher than those in S.reticulata var.mandshurica.The quantum yield of PSII reaction center(APSII)declined in S.reticulata and light capture efficiency(Fv 0/Fm 0)was stable.However,reduction percentages of Fv 0/Fm 0,APSII,and Fv/Fm in S.oblata were significant higher than those of S.reticulata var.mandshurica.After nine hours of chilling,the relative variable fluorescence of VJ and VI of S.oblata increased and the increasing rate of VJ was greater than VI.In contrast,the change of VJ and VI in S.reticulata var.mandshurica leaves was relatively small.This suggests that chilling primarily damaged the electron transport process of QA to QB at the receptor site of the PSII reaction center.Photosynthetic capacity of S.oblata was more sensitive to chilling stress compared to S.reticulate var.mandshurica,which the limitations were mainly due to non-stomatal factors such as the decrease in electron transport efficiency,activity in the PSII reaction center,and the destruction of the photodamage defense system.展开更多
With the widespread application of the computer and microelectronic technology in the industry,digitization becomes the inevitable developing trend of the hydraulic technology.Digitization of the hydraulic components ...With the widespread application of the computer and microelectronic technology in the industry,digitization becomes the inevitable developing trend of the hydraulic technology.Digitization of the hydraulic components is critical in the digital hydraulic technology.High-speed on-of valves(HSVs)which convert a train of input pulses into the fast and accurate switching between the on and of states belong to widely used basic digital hydraulic elements.In some ways,the characteristics of the HSVs determine the performance of the digital hydraulic systems.This paper discusses the development of HSVs and their applications.First,the HSVs with innovative structures which is classifed into direct drive valves and pilot operated valves are discussed,with the emphasis on their performance.Then,an overview of HSVs with intelligent materials is presented with considering of the switching frequency and fow capacity.Finally,the applications of the HSVs are reviewed,including digital hydraulic components with the integration of the HSVs and digital hydraulic systems controlled by the HSVs.展开更多
The distribution of metallic elements in a submerged membrane bioreactor(MBR) was revealed at different temperatures using inductively coupled plasma-optical emission spectrometry(ICP-OES), and the role of extracellul...The distribution of metallic elements in a submerged membrane bioreactor(MBR) was revealed at different temperatures using inductively coupled plasma-optical emission spectrometry(ICP-OES), and the role of extracellular polymeric substances(EPS) was probed by integrating scanning electron microscopy(SEM) with confocal laser scanning microscopy(CLSM) over long-term operation. More metallic elements in the influent were captured by suspended sludge and built up in the fouling layer at lower temperature. The concentration of metallic elements in the effluent was 5.60 mg/L at 10°C operational temperature, far lower than that in the influent(51.35 mg/L). The total contents of metallic elements in suspended sludge and the membrane fouling layer increased to 40.20 and 52.19 mg/g at 10°C compared to 35.14 and 32.45 mg/g at 30°C, and were dominated by the organically bound fraction. The EPS contents in suspended sludge and membrane fouling layer sharply increased to 37.88 and 101.51 mg/g at 10°C, compared to 16.87 and 30.03 mg/g at 30°C. The increase in EPS content at lower temperature was responsible for the deposition of more metallic ions. The strong bridging between EPS and metallic elements at lower temperature enhanced the compactness of the fouling layer and further decreased membrane flux. This was helpful for understanding the mechanism of membrane fouling at different operational temperatures and the role of EPS, and also of significance for the design of cleaning strategies for fouled membranes after long-term operation.展开更多
AIM To determine the role of intravoxel incoherent motion(IVIM) diffusion-weighted(DW) magnetic resonance imaging(MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model.M...AIM To determine the role of intravoxel incoherent motion(IVIM) diffusion-weighted(DW) magnetic resonance imaging(MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model.METHODS Mice bearing MKN-45 human gastric adenocarcinoma xenografts were divided into four treated groups(TG1, 2, 3 and 4, n = 5 in each group) which received Fluorouracil and Calcium Folinate and a control group(CG, n = 7). DW-MRI scans with 14 b-values(0-1500 s/mm2) were performed before and after treatment on days 3, 7, 14 and 21. Fast diffusion component(presumably pseudo-perfusion) parameters including the fast diffusion coefficient(D*) and fraction volume(f p), slow diffusion coefficient(D) and the conventional apparent diffusion coefficients(ADC) were calculated by fitting the IVIM model to the measured DW signals. The median changes from the baseline to each posttreatment time point for each measurement(ΔADC, ΔD* and Δf p) were calculated. The differences in the median changes between the two groups were compared using the mixed linear regression model by the restricted maximum likelihood method shown as z values. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. The median percentage changes were compared with the histopathological analyses between the pre-and post-treatment for each measurement.RESULTS Compared with the control group, D* in the treated group decreased significantly(ΔD*treated% =-30%,-34% and-20%, with z =-5.40,-4.18 and-1.95. P = 0.0001, 0.0001 and 0.0244) and f p increased significantly(Δfptreated% = 93%, 113% and 181%, with z = 4.63, 5.52, and 2.12, P = 0.001, 0.0001 and 0.0336) on day 3, 7 and 14, respectively. Increases in ADC in the treated group were higher than those in the control group on days 3 and 14(z = 2.44 and 2.40, P = 0.0147 and P = 0.0164). CONCLUSION Fast diffusion measurements derived from the biexponential IVIM model may be more sensitive imaging biomarkers than ADC to assess chemotherapy response in gastric adenocarcinoma.展开更多
基金support from the National Key R&D Program of China(2023YFA0913902)the National Natural Science Foundation of China(32088101,22074140,and 22474136)the Dalian Institute of Chemical Physics,Chinese Academy of Sciences(DICP-I202316).
文摘Golgi apparatus(GA)-associated secretome runs through the endomembrane system and is critical for inter-and intracellular communication networks.However,achieving in situ dissection of the GA-associated secretome remains challenging owing to the scarcity of specific labeling methods.This work develops an aggregation-induced emission(AIE)luminogen-mediated photocatalytic proximity labeling strategy that allows profiling of the GA-associated secretome with high spatiotemporal precision.Leveraging an AIE luminogen-derived GA-targeting photocatalyst,this strategy achieves efficient labeling of proteins in minutes within the Golgi lumen upon light activation,which enables spatiotemporally resolved modification of histidine and tyrosine residues.We succeed in profiling secretome in both living HeLa cells and hard-to-transfect macrophage HMC3 cells,and a significant subset of GA-associated secretome with 80%specificity is determined,linking the distinct GA-associated secretory profiles to cellular characteristics.The method is further applied to proteome mapping of brain and bone metastatic lung cancer cells,which reveals the underlying roles the GA-associated secretome plays in extracellular matrix organization during metastasis.This work delivers a robust tool to break the dilemma of chemical labeling of GA-associated secretome in living cells,and provides mechanistic insights into secretion regulation at the subcellular level.
文摘核型分析作为产前诊断常规项目应用于遗传学诊断和遗传咨询。染色体多态性在核型分析中很常见,但因缺乏以图示为参照的多态性判断标准,使各实验室对同一染色体变异是否应判断为多态性以及用什么符号表达多态性存在差异,从而影响核型分析报告的互认及多态性的临床解读。本共识通过采集已确诊的各种多态性核型图,研究其在不同显带技术中的形态特征,比较各种多态性的G带、C带和N带的特征异同,确认多态性G带特征,并参照《人类细胞基因组学国际命名体系(ISCN 2024)》(An International System for Human Cytogenomic Nomenclature,ISCN 2024)进行多态性归类,提出判断标准、鉴别流程、知情告知和临床解读模式,以规范多态性判别,促进核型分析报告互认,确保遗传咨询结果一致,解决本行业长期困扰的多态性判断标准缺乏和同一多态性被不同解读的遗传咨询问题。
基金funded by Jilin Province Science and Technology Development Plan Project,grant number 20220203163SF.
文摘With the increasing integration of large-scale distributed energy resources into the grid,traditional distribution network optimization and dispatch methods struggle to address the challenges posed by both generation and load.Accounting for these issues,this paper proposes a multi-timescale coordinated optimization dispatch method for distribution networks.First,the probability box theory was employed to determine the uncertainty intervals of generation and load forecasts,based on which,the requirements for flexibility dispatch and capacity constraints of the grid were calculated and analyzed.Subsequently,a multi-timescale optimization framework was constructed,incorporating the generation and load forecast uncertainties.This framework included optimization models for dayahead scheduling,intra-day optimization,and real-time adjustments,aiming to meet flexibility needs across different timescales and improve the economic efficiency of the grid.Furthermore,an improved soft actor-critic algorithm was introduced to enhance the uncertainty exploration capability.Utilizing a centralized training and decentralized execution framework,a multi-agent SAC network model was developed to improve the decision-making efficiency of the agents.Finally,the effectiveness and superiority of the proposed method were validated using a modified IEEE-33 bus test system.
文摘Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in millions of fatalities each year.Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication,their ability to reduce hepatitis B surface antigen(HBsAg)levels in plasma remains limited.The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions,rendering long-term administration challenging.Therefore,current drug development efforts for chronic hepatitis B aim to achieve a functional cure,which is defined as HBsAg serological clearance and sustained suppression of HBV DNA.This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors,monoclonal antibodies,RNA interferences,and other agents that directly target the virus.Furthermore,we discuss the development of immunomodulatory therapies,including TLR-7/8 agonists,immune checkpoint inhibitors,and therapeutic vaccines.In the end,we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.
基金supported by National Natural Science Foundation of China(82374296,82271965,62331021)Development Project of Shanghai Peak Disciplines-Integrated Medicine(201801)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Shanghai Municipal Science and Technology Explorer Project(23TS1400500).
文摘Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.
基金National Key Research and Development Program of China,Grant/Award Number:2022YFC2904100National Natural Science Foundation of China,Grant/Award Number:5220409Beijing Noval Program,Grant/Award Number:20230484242。
文摘The Maoping lead–zinc mining area is a significant metal mine site in northeastern Yunnan.In this study,both hydraulic fracturing in situ stress testing and ultrasonic imaging logging were first carried out in the mining area.Second,930 focal mechanism solutions and 231 sets of stress data near the mining area were collected.Then,the variations in the type of in situ stress field,the magnitude of in situ stress,the direction of horizontal principal stress,and the ratio of lateral pressure were analyzed to characterize the distribution of the in situ stress field.On this basis,a new method using borehole breakouts and drilling-induced fractures was proposed to determine the stress direction.Finally,the evolution of the mechanical properties of dolomite with burial depth was analyzed and the influence of rock mechanical properties on the distributions of the in situ stress field was explored.The results show that the in situ stress in the mining area isσ_(H)>σ_(V)>σ_(h),indicating a strike–slip stress state.The in situ stress is high in magnitude,and its value increases with burial depth.The maximum and minimum horizontal lateral stress coefficients are stabilized at approximately 1.22 and 0.73,respectively.The direction of the maximum horizontal principal stress is NW,mainly ranging from N58.44°W to N59.70°W.The stress field inferred from the focal mechanism solution is in good agreement with the test results.The proportion of structural planes with dip angles between 30°and 75°exceeds 80%,and the dip direction of the structural planes is mainly NW to NWW.The line density of structural planes shows high density in shallow areas and low density in deep areas.More energy tends to be accumulated in rocks with higher elastic modulus and strength,leading to higher in situ stress levels.These findings are of significant reference for mine tunnel layout,support design optimization,and disaster prevention.
基金supported by the National Natural Science Foundation of China[No.81871823,8207090113,82072510]National Key R&D Program of China[No.2018YFC1312900]+2 种基金Shanghai Natural Science Foundation[No.20ZR1406400]Science and Technology Commission of Shanghai Municipality[No.18JC1410403]Shanghai Municipal Science and Technology Major Project[No.2017SHZDZX01,2018SHZDZX01].
文摘Purpose Lateral ankle sprains(LAS)are associated with corticospinal pathway deficits.Existing evidence is primarily based on cross-sectional investigations and noncausal speculations.This study aims to determine whether maladaptive corticospinal pathway alterations occur pre-and postligament transection in LAS mouse models.Additionally,this study explores whether the alterations are more pronounced in adolescent mice than adults.Methods Twenty-four 8-week-old adolescent and twenty-four 24-week-old adult mice were randomly assigned to lateral ankle ligament transection or sham surgery.Diffusion-weighted imaging of the corticospinal pathway was performed presurgery and 8 weeks postsurgery.Fractional anisotropy(FA)values,reflecting fiber integrity within the corticospinal subregions of the medulla,pons,midbrain,and cerebrum,were extracted.Results Overall,41 mice completed repeated image acquisition.Before surgery,no significant group effects on FA within the four corticospinal subregions were detected in either adolescent or adult mice.Two months after surgery,the adolescent cohort displayed a significant reduction in FA in the medulla subregion following ankle ligament transection(β-baseline-adjusted=-0.083,95%CI,-0.145 to-0.021,p-corrected=0.048).Conversely,no significant effects of ankle ligament transection on corticospinal FA were observed in the adult cohort.Conclusion The maladaptive alterations in the corticospinal tract could be observed in the adolescent LAS mouse model,characterized by reduced fiber integrity in the medulla subregion.While these results are derived from an animal model,they provide a foundation for future investigations into the mechanisms underlying neurological deficits following musculoskeletal injuries.
基金funded,in part,by a Ball State University ASPiRE grant.
文摘Older adults are at an increased risk of developing knee osteoarthritis.High internal knee abduction moment during daily activities may elevate the risk of knee osteoarthritis.Incline walking exercise has been found to decrease knee abduction moment in healthy young adults.However,it is unknown if this occurs in healthy older adults.The purpose of this study was to quantify the internal knee abduction moment at different treadmill grades to determine if incline walking could reduce the knee abduction moment in healthy older adults.Twelve healthy older adult males walked on a treadmill at five incline grades(0%,5%,10%,15%,and 20%)at 1.34 m·s^(-1).The primary outcome variable was the internal knee abduction moment.A one-way repeated measures multivariate analysis of variance was performed to determine differences in the dependent variables among incline gradients.Peak knee abduction moment significantly decreased from level walking at all gradients in 10% increments(0%-10%,p<0.001;5%-15%,p<0.002;and 10%-20%,p=0.04).A reduction in knee abduction moment during incline walking could result in decreased knee joint loading on the medial knee compartment.For older adults,who are looking to exercise to improve their health,incline walking may be beneficial to promote lower body strength and cardiovascular ability without inflicting further harm to the aging knee joints.However,because the frontal plane knee joint was of primary interest in this study,further research is needed to determine the effects of incline walking on other joints and in other planes of motion.
文摘This article explores the role of distributed energy resources such as efficient solar cells that drive carbon neutrality within the solar energy. For example, the perovskite solar cells offer high efficiency and potential for low-cost production. A novel theoretical model is discovered in distributed energy resources for power emissions and cost. The smart carbon neutrality approaches are analyzed in both theory and experiments. The advantages, current challenges, and future prospects of the related solutions are discussed methodically. By addressing stability and scalability issues, these approaches can contribute significantly to reducing carbon emissions and promoting sustainable energy solutions.
基金supported by the National Key Research and Development Program of China(2021YFC2203004)the National Natural Science Foundation of China(NSFC)(12405076,12247187,and 12147103)+1 种基金the National Astronomical Data Center(NADC2023YDS-01)the Fundamental Research Funds for the Central Universities.
文摘The detection of gravitational waves by the LIGO-Virgo-KAGRA collaboration has ushered in a new era of observational astronomy,emphasizing the need for rapid and detailed parameter estimation and population-level analyses.Traditional Bayesian inference methods,particularly Markov chain Monte Carlo,face significant computational challenges when dealing with the high-dimensional parameter spaces and complex noise characteristics inherent in gravitational wave data.This review examines the emerging role of simulation-based inference methods in gravitational wave astronomy,with a focus on approaches that leverage machine-learning techniques such as normalizing flows and neural posterior estimation.We provide a comprehensive overview of the theoretical foundations underlying various simulation-based inference methods,including neural posterior estimation,neural ratio estimation,neural likelihood estimation,flow matching,and consistency models.We explore the applications of these methods across diverse gravitational wave data processing scenarios,from single-source parameter estimation and overlapping signal analysis to testing general relativity and conducting population studies.Although these techniques demonstrate speed improvements over traditional methods in controlled studies,their model-dependent nature and sensitivity to prior assumptions are barriers to their widespread adoption.Their accuracy,which is similar to that of conventional methods,requires further validation across broader parameter spaces and noise conditions.
基金supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China,No.2017LH0301(to JXJ),2016MS08108(to ZJY)Science and Technology Planning Project of Inner Mongolia Autonomous Region of China,No.201602069(to ZJY)+1 种基金PhD Scientific Research Fund of Baotou Medical College of China,No.BSJJ201606(to JXJ)"Dengfeng Project" Scientific Research Fund of Baotou Medical College of China,No.BYJJ-DF 201703(to JXJ)
文摘Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.
基金supported by the National Basic Research Program(973)of China(No.2009CB426301)the National Natural Science Foundation of China(No.40773076,40703026)
文摘This work investigated the distribution and speciation of Cd,Cu,Pb,Fe and Mn in the shallow sediments of Jinzhou Bay,Northeast China,which has been heavily contaminated by nonferrous smelting activities.The concentrations of Cd,Cu and Pb in sediments were found to be 100,13 and 7 times,respectively,being higher than the national guideline(GB 18668-2002).Sequential extraction test showed that 39%-61%of Cd were exchangeable fractions,indicating that Cd in the sediments posed a high risk to local environments.While Cu and Pb were at moderate risk levels.According to the relationships between percentage of metal speciation and total metal concentration,it was concluded that the distributions of Cd,Cu and Pb in some geochemical fractions were dynamic in the process of pollutants migration and the stability of metals in sediments of Jinzhou Bay decreased in the order of Pb〉Cu〉Cd.
基金supported by the National Natural Science Foundation of China[grant numbers 82372492,82072510]National Key R&D Program of China[grant numbers 2018YFC1312900]+1 种基金Shanghai Natural Science Foundation[grant numbers 20ZR1406400]Science and Technology Commission of Shanghai Municipality[grant numbers 22dz1204700].
文摘Purpose:Ankle proprioception deficits have been widely reported in patients with chronic ankle instability(CAI),but their central neuropathological mechanisms have not been fully discussed.So,we aimed to figure out whether the structural and functional features of the cerebellar vermis differed between patients with CAI and healthy controls,and are associated with proprioception deficits in patients.Methods:Twenty-two patients and 25 control individuals were enrolled in a cross-sectional investigation.All participants underwent structural and resting-state functional magnetic resonance imaging scanning to calculate voxel-based morphometry(VBM)and fractional amplitude of low-frequency fluctuation(fALFF)of the vermis.Between-group comparisons of the ankle instability-related subregions of the vermis were performed.Correlation analyses were performed between the outcomes of the surviving subregions and the proprioceptive scores of the ankle inversion discrimination apparatus for landing test.Results:The subregion of vermis Ⅳ/Ⅴ survived the multiple comparison correction to reveal a lower VBM value in patients than in healthy controls(Cohen's d=-0.968).The patients also showed significantly higher fALFF(Cohen's d=0.666)in this subregion.After controlling the demographic features,the proprioceptive scores were significantly correlated with VBM(r=0.622)and fALFF values(r=-0.512)in the group of patients.Conclusions:Patients with CAI have lower gray matter volume and higher activity intensity in the cerebellar vermis than healthy control.The more severe proprioception deficits were significantly associated with the vermal volume and activity,which might be able to facilitate future diagnoses and treatments for CAI.
基金This project was granted by the National Nature Science Foundation of China(No.30100185).
文摘Aim： To explore the effect of androgen receptor （AR） on the expression of the cell cycle-related genes, such as CDKNIA and BTG1, in prostate cancer cell line LNCaP. Methods： After AR antagonist flutamide treatment and confirmation of its effect by phase contrast microscope and flow cytometry, the differential expression of the cell cycle-related genes was analyzed by a cDNA microarray. The flutamide treated cells were set as the experimental group and the LNCaP cells as the control. We labeled cDNA probes of the experimental group and control group with Cy5 and Cy3 dyes, respectively, through reverse transcription. Then we hybridized the cDNA probes with cDNA microarrays, which contained 8 126 unique human cDNA sequences and the chip was scanned to get the fluorescent values of Cy5 and Cy3 on each spot. After primary analysis, reverse transcription polymerase chain reaction （RT- PCR） tests were carried out to confirm the results of the chips. Results：After AR antagonist flutamide treatment, three hundred and twenty-six genes （3.93 %） expressed differentially, 97 down-regulated and 219 up-regulated. Among them, eight up-regulated genes might be cell cycle-related, namely CDCIO, NRAS, BTG1, Wee1, CLK3, DKFZP564A122, CDKNIA and BTG2. The CDKNIA and BTG1 gene mRNA expression was confirmed to be higher in the experimental group by RT-PCR, while p53 mRNA expression had no significant changes. Conclusion： Flutamide treatment might up-regulate CDKN1A and BTG1 expression in prostate cancer cells. The protein expressions of CDKN1A and BTG1 play an important role in inhibiting the proliferation of cancer cells. CDKN1A has a great impact on the cell cycle of prostate cancer cells and may play a role in the cancer cells in a p53-independent pathway. The prostate cancer cells might affect the cell cycle-related genes by activating AR and thus break the cell cycle control.
文摘Syringa species not only have good ornamental properties but also play an important role in the landscaping and environmental purification of cities.To investigate the chilling stress resistance of Syringa oblata Lindl.and Syringa reticulata var.mandshurica and provide theoretical grounds for the practical cultivation of Syringa species,in vitro leaves were used to study photosynthetic gas exchange parameters and chlorophyll fluorescence parameters.After nine hours of chilling,decreasing rates of net photosynthesis,stomatal conductance,and transpiration in S.reticulata var.mandshurica leaves were significantly greater than that of the S.oblata,while intercellular CO2 concentrations in S.oblata leaves were higher than those in S.reticulata var.mandshurica.The quantum yield of PSII reaction center(APSII)declined in S.reticulata and light capture efficiency(Fv 0/Fm 0)was stable.However,reduction percentages of Fv 0/Fm 0,APSII,and Fv/Fm in S.oblata were significant higher than those of S.reticulata var.mandshurica.After nine hours of chilling,the relative variable fluorescence of VJ and VI of S.oblata increased and the increasing rate of VJ was greater than VI.In contrast,the change of VJ and VI in S.reticulata var.mandshurica leaves was relatively small.This suggests that chilling primarily damaged the electron transport process of QA to QB at the receptor site of the PSII reaction center.Photosynthetic capacity of S.oblata was more sensitive to chilling stress compared to S.reticulate var.mandshurica,which the limitations were mainly due to non-stomatal factors such as the decrease in electron transport efficiency,activity in the PSII reaction center,and the destruction of the photodamage defense system.
基金Supported by Key Technologies Research and Development Program of China(Grant No.2019YFB2004502)National Natural Science Foundation of China(Grant Nos.51805350,51775362)Postdoctoral Science Foundation of China(Grant No.2019M651073).
文摘With the widespread application of the computer and microelectronic technology in the industry,digitization becomes the inevitable developing trend of the hydraulic technology.Digitization of the hydraulic components is critical in the digital hydraulic technology.High-speed on-of valves(HSVs)which convert a train of input pulses into the fast and accurate switching between the on and of states belong to widely used basic digital hydraulic elements.In some ways,the characteristics of the HSVs determine the performance of the digital hydraulic systems.This paper discusses the development of HSVs and their applications.First,the HSVs with innovative structures which is classifed into direct drive valves and pilot operated valves are discussed,with the emphasis on their performance.Then,an overview of HSVs with intelligent materials is presented with considering of the switching frequency and fow capacity.Finally,the applications of the HSVs are reviewed,including digital hydraulic components with the integration of the HSVs and digital hydraulic systems controlled by the HSVs.
基金supported by the National Key Research and Development Program (No.2016YFC0400707)the Research and Innovation Project for Postgraduates of Higher Education Institutions of Jiangsu Province (Nos.KYLX16_0812 and SJZZ16_0216)
文摘The distribution of metallic elements in a submerged membrane bioreactor(MBR) was revealed at different temperatures using inductively coupled plasma-optical emission spectrometry(ICP-OES), and the role of extracellular polymeric substances(EPS) was probed by integrating scanning electron microscopy(SEM) with confocal laser scanning microscopy(CLSM) over long-term operation. More metallic elements in the influent were captured by suspended sludge and built up in the fouling layer at lower temperature. The concentration of metallic elements in the effluent was 5.60 mg/L at 10°C operational temperature, far lower than that in the influent(51.35 mg/L). The total contents of metallic elements in suspended sludge and the membrane fouling layer increased to 40.20 and 52.19 mg/g at 10°C compared to 35.14 and 32.45 mg/g at 30°C, and were dominated by the organically bound fraction. The EPS contents in suspended sludge and membrane fouling layer sharply increased to 37.88 and 101.51 mg/g at 10°C, compared to 16.87 and 30.03 mg/g at 30°C. The increase in EPS content at lower temperature was responsible for the deposition of more metallic ions. The strong bridging between EPS and metallic elements at lower temperature enhanced the compactness of the fouling layer and further decreased membrane flux. This was helpful for understanding the mechanism of membrane fouling at different operational temperatures and the role of EPS, and also of significance for the design of cleaning strategies for fouled membranes after long-term operation.
文摘AIM To determine the role of intravoxel incoherent motion(IVIM) diffusion-weighted(DW) magnetic resonance imaging(MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model.METHODS Mice bearing MKN-45 human gastric adenocarcinoma xenografts were divided into four treated groups(TG1, 2, 3 and 4, n = 5 in each group) which received Fluorouracil and Calcium Folinate and a control group(CG, n = 7). DW-MRI scans with 14 b-values(0-1500 s/mm2) were performed before and after treatment on days 3, 7, 14 and 21. Fast diffusion component(presumably pseudo-perfusion) parameters including the fast diffusion coefficient(D*) and fraction volume(f p), slow diffusion coefficient(D) and the conventional apparent diffusion coefficients(ADC) were calculated by fitting the IVIM model to the measured DW signals. The median changes from the baseline to each posttreatment time point for each measurement(ΔADC, ΔD* and Δf p) were calculated. The differences in the median changes between the two groups were compared using the mixed linear regression model by the restricted maximum likelihood method shown as z values. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. The median percentage changes were compared with the histopathological analyses between the pre-and post-treatment for each measurement.RESULTS Compared with the control group, D* in the treated group decreased significantly(ΔD*treated% =-30%,-34% and-20%, with z =-5.40,-4.18 and-1.95. P = 0.0001, 0.0001 and 0.0244) and f p increased significantly(Δfptreated% = 93%, 113% and 181%, with z = 4.63, 5.52, and 2.12, P = 0.001, 0.0001 and 0.0336) on day 3, 7 and 14, respectively. Increases in ADC in the treated group were higher than those in the control group on days 3 and 14(z = 2.44 and 2.40, P = 0.0147 and P = 0.0164). CONCLUSION Fast diffusion measurements derived from the biexponential IVIM model may be more sensitive imaging biomarkers than ADC to assess chemotherapy response in gastric adenocarcinoma.
