Organoids possess immense potential for unraveling the intricate functions of human tissues and facilitating preclinical disease treatment.Their applications span from high-throughput drug screening to the modeling of...Organoids possess immense potential for unraveling the intricate functions of human tissues and facilitating preclinical disease treatment.Their applications span from high-throughput drug screening to the modeling of complex diseases,with some even achieving clinical translation.Changes in the overall size,shape,boundary,and other morphological features of organoids provide a noninvasive method for assessing organoid drug sensitivity.However,the precise segmentation of organoids in bright-field microscopy images is made difficult by the complexity of the organoid morphology and interference,including overlapping organoids,bubbles,dust particles,and cell fragments.This paper introduces the precision organoid segmentation technique(POST),which is a deep-learning algorithm for segmenting challenging organoids under simple bright-field imaging conditions.Unlike existing methods,POST accurately segments each organoid and eliminates various artifacts encountered during organoid culturing and imaging.Furthermore,it is sensitive to and aligns with measurements of organoid activity in drug sensitivity experiments.POST is expected to be a valuable tool for drug screening using organoids owing to its capability of automatically and rapidly eliminating interfering substances and thereby streamlining the organoid analysis and drug screening process.展开更多
To address the challenges of high energy consumption and prominent costs in the traditional three-columns distillation process for cellulosic fuel ethanol,a distillation–molecular sieve coupling separation process is...To address the challenges of high energy consumption and prominent costs in the traditional three-columns distillation process for cellulosic fuel ethanol,a distillation–molecular sieve coupling separation process is proposed.This process integrates a three-column(crude distillation column,first distillation column,second distillation column)system with a 3A molecular sieve adsorption deep dehydration unit.A thermal coupling network is constructed via differential pressure design(steam from medium/high-pressure columns as mutual heat sources,reboiler liquid waste heat for feed preheating),and molecular sieve adsorption conditions are optimized.The study first performs a thermodynamic consistency test on the ethanol–water system,determines optimal non-random two-liquid(NRTL)model binary interaction parameters via experimental data regression for Aspen Plus simulation.Aiming at minimum total annual cost(TAC),Aspen Plus is used to optimize process parameters(theoretical tray number,feed location,reflux ratio,side-draw position,etc.).Economic analysis shows this process reduces CO_(2) emission costs by 27.56%,TAC by 15.58%(to 5.123×10^(6) USD·a^(−1)),and increases ethanol purity to>99.6%,providing an effective solution for green,efficient separation.展开更多
[Objectives]This study was conducted to establish a quantitative assessment method for the textural quality of chieh-qua fruit.[Methods]Using two modes of a texture analyzer,namely TPA(texture profile analysis)and pun...[Objectives]This study was conducted to establish a quantitative assessment method for the textural quality of chieh-qua fruit.[Methods]Using two modes of a texture analyzer,namely TPA(texture profile analysis)and puncture,the index data of the fruit were obtained by setting different trigger forces,deformation levels,test speeds,as well as puncture speeds and puncture depths.The data included TPA hardness,adhesiveness,springiness,cohesiveness,gumminess,chewiness,resilience,as well as skin hardness,skin toughness,flesh hardness,fracturability,and compactness.[Results]Different deformation levels had a significant impact on all parameters.Hardness,adhesiveness,gumminess and chewiness showed a trend of first increasing and then decreasing with the deformation level increasing.When the deformation level was 30%,the adhesiveness,gumminess and chewiness reached their maximum values.When the deformation level was 50%,TPA hardness reached its maximum.When the compression speed was 3 mm/s,the measured values of TPA hardness,adhesiveness,chewiness,and resilience were at their maximums.The skin hardness varied significantly under different trigger forces.When the trigger force was 15 g,the skin hardness reached a maximum value of 944.63 g,and the skin toughness,flesh hardness,fracturability,and compactness also reach their maximum values respectively.When the puncture depth was 12 mm,the flesh hardness and skin toughness reached their maximums of 682.51 g and 1.82 mm,respectively.In the TPA mode,the flesh hardness of chieh-qua showed an extremely significant negative correlation with springiness,cohesiveness,and resilience(P<0.01).The fruit fracturability detected by puncture had an extremely significant positive correlation with compactness(P<0.01).[Conclusions]The evaluation method for measuring chieh-qua texture by combining TPA and the puncture mode could accurately and quantitatively reflect the differences in the flesh texture quality of chieh-qua.The optimal parameters for texture measurement of chieh-qua fruit were determined as a 15 g trigger force with 50%deformation and a 3 mm/s compression speed in TPA mode,and a 15 g trigger force with a 12 mm puncture depth in puncture mode.Puncture speed was found to have no significant effect on the texture indices of chieh-qua.展开更多
In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a persona...In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a personal exposure study was conducted for school children, and office workers in Beijing, China. For all participants （N = 114）, the mean personal 24-hr exposure concentration was 102.5, 14.7, 0.093, 0.528, 0.934, 0.174 and 0.703 μg/m 3 for PM 2.5 , black carbon, Mn, Al, Ca, Pb, and Fe. Children’s exposure concentrations of PM 2.5 were 4–5 times higher than those in related studies. The ambient concentration of PM 2.5 （128.5 μg/m 3 ） was significantly higher than the personal exposure concentration （P 0.05）, and exceed the reference concentration （25 μg/m 3 ） of WHO air quality guideline. Good correlation relationships and significant differences were identified between ambient concentration and personal exposure concentration. The relationships indicate that the ambient concentration is the main factor influencing personal exposure concentration, but is not a good indicator of personal exposure concentration. Outdoor activities （commute mode, exposure to heating, workday or weekend travel） influenced personal exposure concentrations significantly, but the magnitude of the influence from indoor activities （exposure to cooking） was masked by the high ambient concentrations.展开更多
This study employed the Box-Behnken design in response surface methodology(RSM)to optimize predistillation and pressurized distillation column parameters in methanol distillation.Statistical and fittinganalyses demons...This study employed the Box-Behnken design in response surface methodology(RSM)to optimize predistillation and pressurized distillation column parameters in methanol distillation.Statistical and fittinganalyses demonstrated the effects of operational parameters and their interactions on product purity and operating costs.Results showed that for methanol mass fraction in the product,the top distillate of the predistillation column(D_(1)),the interaction between D_(1) and the top distillate of the pressurized distillation column(D_(2)),and the interaction between the theoretical plates of the pressurized distillation column(N_(2))and its refluxratio(R_(2))significantlyaffected the outcome,in addition to pressurized distillation column parameters.Acetone mass fraction was mainly influencedby predistillation column parameters and their interactions,with minimal relation to the pressurized distillation column.Operating costs were primarily affected by the refluxratio(R),withdrawal(D)of both columns,and their interactions.Optimization strategies involved increasing theoretical plates and reducing refluxratios compared to the initial plan,achieving energy-saving and consumption-reduction goals.The process required the pressurized distillation column‘s methanol mass fraction to exceed 99.80%,acetone mass fraction below 2×10^(-8),and formaldehyde mass fraction below 5×10^(-9),with a feed rate of 6100 kg·h^(-1).Plans A,B,and C achieved energy-savings of 29.80%,21.78%,and 25.50%respectively,while ensuring separation efficiencyand product quality.This research provides theoretical and practical guidance for optimizing the methanol distillation process,helping to reduce energy consumption and production costs,thereby enhancing corporate competitiveness.展开更多
In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth char...In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.展开更多
BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2D...BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2DM)are considered to have a predisposition to hepatic steatosis.However,the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University,who underwent MR mDIXONQuant examination to quantify the hepatic fat fraction(HFF).According to body mass index(BMI),the patients were divided into normal weight,overweight,and obese groups.The differences in general statistics,biochemical parameters,islet function,and HFF were compared among the three groups.The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.RESULTS The HFF of T2DM patients gradually increased in the normal weight,overweight,and obese groups(P<0.05).Spearman correlation analysis showed that in T2DM patients,HFF was negatively correlated with age and high-density lipoprotein cholesterol(P<0.05),whereas it was positively correlated with BMI,waist-hip ratio,fasting plasma glucose,alanine aminotransferase(ALT),aspartate aminotransferase,bilirubin,glutamyl transpeptidase,lactate dehydrogenase,albumin(ALB),uric acid(UA),total cholesterol,TG,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,free triiodothyronine,fasting insulin,fasting C-peptide,and homeostasis model assessment of insulin resistance(P<0.05).Multiple linear regression analysis showed significant positive influences of BMI,ALT,LDL-C,UA,and ALB on HFF in T2DM patients(P<0.05).Binary logistic regression analysis showed that BMI,ALT,ALB,and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients,and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times(P<0.05).CONCLUSION The HFF of T2DM patients increases with BMI.Higher BMI,ALT,ALB,and LDLC are independent risk factors for moderate to severe fatty liver in T2DM patients.展开更多
BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the...BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ(AIS).METHODS This study enrolled 43 patients with T2DM combined with lung AIS(T2DM+AIS group),43 patients with T2DM alone(T2DM group),43 patients with lung AIS alone(AIS group),and 43 healthy volunteers(control group).The serum levels of vWF,insulin-like growth factor 1,and insulin-like growth factor binding protein 3 were determined.Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTS Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(P<0.05).Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group(P<0.05).There was no significant difference in serum vWF level between the T2DM and AIS groups.In the T2DM+AIS group,serum vWF was independently associated and positively correlated with serum levels of insulinlike growth factor 1 and insulin-like growth factor binding protein 3(P<0.05).CONCLUSION Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.展开更多
Exploring suitable high-capacity V_(2)O_(5)-based cathode materials is essential for the rapid advancement of aqueous zinc ion batteries(ZIBs).However,the typical problem of slow Zn^(2+)diffusion kinetics has severely...Exploring suitable high-capacity V_(2)O_(5)-based cathode materials is essential for the rapid advancement of aqueous zinc ion batteries(ZIBs).However,the typical problem of slow Zn^(2+)diffusion kinetics has severely limited the feasibility of such materials.In this work,unique hydrated vanadates(CaVO,BaVO)were obtained by intercalation of Ca^(2+)or Ba^(2+)into hydrated vanadium pentoxide.In the CaVO//Zn and BaVO//Zn batteries systems,the former delivered up to a 489.8 mAh g^(-1)discharge specific capacity at 0.1 A g^(-1).Moreover,the remarkable energy density of 370.07 Wh kg^(-1)and favorable cycling stability yard outperform BaVO,pure V_(2)O_(5),and many reported cathodes of similar ionic intercalation compounds.In addition,pseudocapacitance analysis,galvanostatic intermittent titration(GITT)tests,and Trasatti analysis revealed the high capacitance contribution and Zn^(2+)diffusion coefficient of CaVO,while an in-depth investigation based on EIS elucidated the reasons for the better electrochemical performance of CaVO.Notably,ex-situ XRD,XPS,and TEM tests further demonstrated the Zn^(2+)insertion/extraction and Zn-storage mechanism that occurred during the cycle in the CaVO//Zn battery system.This work provides new insights into the intercalation of similar divalent cations in vanadium oxides and offers new solutions for designing cathodes for high-capacity aqueous ZIBs.展开更多
The(2 + 1)-dimensional Ito equation is extended to a general form including some nonintegrable effects via introducing generalized bilinear operators. It is pointed out that the nonintegrable(2 + 1)-dimensional Ito eq...The(2 + 1)-dimensional Ito equation is extended to a general form including some nonintegrable effects via introducing generalized bilinear operators. It is pointed out that the nonintegrable(2 + 1)-dimensional Ito equation contains lump solutions and interaction solutions between lump and stripe solitons. The result shows that the lump soliton will be swallowed or arisen by a stripe soliton in a fixed time. Furthermore, by the interaction between a lump and a paired resonant stripe soliton, the lump will be transformed to an instanton or a rogue wave.展开更多
The method of density matching between the solid and liquid phases is often adopted to effectively eliminate the effect of sedimentation of suspensions on dynamic behavior of a colloidal system. Experiments on crystal...The method of density matching between the solid and liquid phases is often adopted to effectively eliminate the effect of sedimentation of suspensions on dynamic behavior of a colloidal system. Experiments on crystallization of charged colloidal microspheres with di- ameter of 98 nm dispersed in density-matched and -unmatched media （mixtures of H20 and D20 in proper proportion） are compared to examine the influence of sedimentation. Reflection spectra of colloidal suspensions were used to monitor the crystallization process. Results showed that the crystal size of the density-unmatched （namely, in the presence of sedimentation） sample grew faster than that of the density-matched （in the absence of sedi- mentation） case at the initial stage of the crystallization, and then the latter overtook and outstripped the former. To explain these observations, we assume that in the settling of crystals sedimentation facilitates result in more particles getting into the crystal structures. However, as the crystals increase to varying sizes, the settling velocities become large and hydrodynamic friction strips off some particles from the delicate crystal structures. Overall, the sedimentation appears to accelerate the crystal size growth initially and then retard the growth. In addition, the crystal structures formed under microgravity were more closely packed than that in normal gravity.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a l...BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a lower HBV deoxyribonucleic acid(DNA)load.The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood.AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.METHODS 1603 HBsAg-seropositive patients were included in the study.We first explored the relationship between patients'lipid levels,hepatic steatosis,and HBV DNA load.Also,we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro.By knocking down and overexpressing Plin2,we observed whether Plin2 regulates autophagy and HBV replication.By inhibiting both Plin2 and cellular autophagy under high lipid stimulation,we examined whether the Plin2-autophagy pathway regulates HBV replication.RESULTS The results revealed that serum triglyceride levels,high-density lipoprotein levels,and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group.Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load.Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAgpositive and HBeAg-negative groups.An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism.The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg,HBeAg,and HBV DNA load.Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins.Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy.Knocking down Plin2 and blocking autophagy with 3-methyladenine(3-MA)inhibited HBV DNA replication.CONCLUSION In conclusion,lipid metabolism is a significant factor affecting HBV load in patients with HBV infection.The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.展开更多
Developing high voltage lithium cobalt oxide(LiCoO_(2),LCO)is crucial for attaining the enhanced capacity and energy density of lithium-ion batteries.However,severe interface and structural instability lead to rapid d...Developing high voltage lithium cobalt oxide(LiCoO_(2),LCO)is crucial for attaining the enhanced capacity and energy density of lithium-ion batteries.However,severe interface and structural instability lead to rapid degradation of LCO under the condition of high voltage.Herein,a successful strategy for modifying the interface of LCO is developed using a one-step high temperature process.By coating LCO with Li3TiMg(PO4)3(LTMP),the obtained phosphate can stabilize the surface crystal structure and boost the mechanical stability of LCO.The high temperature process enables the successful doping of Ti/Mg into the LCO lattice,effectively inhibiting the harmful phase transition effect across various voltage ranges.Compared to commercial LCO and the reported studies,the modified LCO@LTMP performs outstanding electrochemical performance.It delivers an initial discharge specific capacity of 216.4 mAh·g^(−1) at 0.1 C and 189.98 mAh·g^(−1) at 1 C.After 250 cycles at 1 C,it preserves 87.46%of its initial capacity,manifesting excellent cycling stability.Moreover,it provides a discharge specific capacity of 115.9 mAh·g^(−1) at 5 C,demonstrating outstanding rate performance.This work holds great potential for practical applications and offers valuable guidance for developing other high performance cathode materials in rechargeable batteries.展开更多
Conservation management practices e including agroforestry,cover cropping,no-till,reduced tillage,and residue return e have been applied for decades to control surface runoff and soil erosion,yet results have not been...Conservation management practices e including agroforestry,cover cropping,no-till,reduced tillage,and residue return e have been applied for decades to control surface runoff and soil erosion,yet results have not been integrated and evaluated across cropping systems.In this study we collected data comparing agricultural production with and without conservation management strategies.We used a bootstrap resampling analysis to explore interactions between practice type,soil texture,surface runoff,and soil erosion.We then used a correlation analysis to relate changes in surface runoff and soil erosion to 13 other soil health and agronomic indicators,including soil organic carbon,soil aggregation,infil-tration,porosity,subsurface leaching,and cash crop yield.Across all conservation management practices,surface runoff and erosion had respective mean decreases of 67%and 80%compared with controls.Use of cover cropping provided the largest decreases in erosion and surface runoff,thus emphasizing the importance of maintaining continuous vegetative cover on soils.Coarse-and medium-textured soils had greater decreases in both erosion and runoff than fine-textured soils.Changes in surface runoff and soil erosion under conservation management were highly correlated with soil organic carbon,aggregation,porosity,infiltration,leaching,and yield,showing that conservation practices help drive important in-teractions between these different facets of soil health.This study offers the first large-scale comparison of how different conservation agriculture practices reduce surface runoff and soil erosion,and at the same time provides new insight into how these interactions influence the improvement or loss of soil health。展开更多
Verticillium wilt disease becomes a major threat to many economically important crops. It is unclear whether and how plant immunity takes place during cotton-Verticillium interaction due to the lack of marker genes. T...Verticillium wilt disease becomes a major threat to many economically important crops. It is unclear whether and how plant immunity takes place during cotton-Verticillium interaction due to the lack of marker genes. Taking advantage of cotton （Gossypium hirsutum） genome, we discovered pathogenesis-related （PR） gene families, which have been widely used as markers of immune responses in plants. To profile the expression of G. hirsutum PR genes in the process of plant immunity, we treated cotton roots with two immunogenic peptides, fig22 and nlp20 known as pathogen-associated molecular patterns, as well as three Verticillium dahliae-derived peptides, nlp20vd2, nlp23vd3, and nlp23vd4 which are highly identical to nlp20. Quantitative real-time PCR results revealed that 14 G. hirsutum PR gene （GhPR） families were induced or suppressed independently in response to fig22, nip20, nlp20va2, nlp23vd3, and nlp23vd4. Most GhPR genes are expressed highest at 3 h post incubation of immunogenic peptides. Compared to fig22 and nlp20, nlp20vd2 is more effective to trigger up-regulated expression of GhPR genes. Notably, both nlp23vd3 and nlp23vd4 are able to induce GhPR gene up-regulation, although they do not induce necrosis on cotton leaves. Thus, our results provide marker genes and new immunogenic peptides for further investigation of cotton-V, dahliae interaction.展开更多
RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMO...RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2(SHH2) is an H3 K9 me1 reader. Our structural studies reveal that H3 K9 me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di-and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a monomethyllysine recognition mechanism which potentially links RdDM to H3 K9 me1 in maize.展开更多
DNA methylation,a conserved epigenetic mark,is critical for tuning temporal and spatial gene expression.The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1(ROS1)initiates active DNA demethylation a...DNA methylation,a conserved epigenetic mark,is critical for tuning temporal and spatial gene expression.The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1(ROS1)initiates active DNA demethylation and is required to prevent DNA hypermethylation at thousands of genomic loci.However,how ROS1 is recruited to specific loci is not well understood.Here,we report the discovery of Arabidopsis AGENET Domain Containing Protein 3(AGDP3)as a cellular factor that is required to prevent gene silencing and DNA hypermethylation.AGDP3 binds to H3K9me2 marks in its target DNA via its AGD12 cassette.Analysis of the crystal structure of the AGD12 cassette of AGDP3 in complex with an H3K9me2 peptide revealed that dimethylated H3 K9 and unmodified H3 K4 are specifically anchored into two different surface pockets.A histidine residue located in the methyllysine binding aromatic cage provides AGDP3 with pH-dependent H3K9me2 binding capacity.Our results uncover a molecular mechanism for the regulation of DNA demethylation by the gene silencing mark H3K9me2.展开更多
基金supported by the National Key R&D Program of China(No.2022YFC2504403)the National Natural Science Foundation of China(No.62172202)+1 种基金the Experiment Project of China Manned Space Program(No.HYZHXM01019)the Fundamental Research Funds for the Central Universities from Southeast University(No.3207032101C3)。
文摘Organoids possess immense potential for unraveling the intricate functions of human tissues and facilitating preclinical disease treatment.Their applications span from high-throughput drug screening to the modeling of complex diseases,with some even achieving clinical translation.Changes in the overall size,shape,boundary,and other morphological features of organoids provide a noninvasive method for assessing organoid drug sensitivity.However,the precise segmentation of organoids in bright-field microscopy images is made difficult by the complexity of the organoid morphology and interference,including overlapping organoids,bubbles,dust particles,and cell fragments.This paper introduces the precision organoid segmentation technique(POST),which is a deep-learning algorithm for segmenting challenging organoids under simple bright-field imaging conditions.Unlike existing methods,POST accurately segments each organoid and eliminates various artifacts encountered during organoid culturing and imaging.Furthermore,it is sensitive to and aligns with measurements of organoid activity in drug sensitivity experiments.POST is expected to be a valuable tool for drug screening using organoids owing to its capability of automatically and rapidly eliminating interfering substances and thereby streamlining the organoid analysis and drug screening process.
基金support from the National Key Research and Development Program of China(2022YFC2106300)the National Natural Science Foundation of China(42177400).
文摘To address the challenges of high energy consumption and prominent costs in the traditional three-columns distillation process for cellulosic fuel ethanol,a distillation–molecular sieve coupling separation process is proposed.This process integrates a three-column(crude distillation column,first distillation column,second distillation column)system with a 3A molecular sieve adsorption deep dehydration unit.A thermal coupling network is constructed via differential pressure design(steam from medium/high-pressure columns as mutual heat sources,reboiler liquid waste heat for feed preheating),and molecular sieve adsorption conditions are optimized.The study first performs a thermodynamic consistency test on the ethanol–water system,determines optimal non-random two-liquid(NRTL)model binary interaction parameters via experimental data regression for Aspen Plus simulation.Aiming at minimum total annual cost(TAC),Aspen Plus is used to optimize process parameters(theoretical tray number,feed location,reflux ratio,side-draw position,etc.).Economic analysis shows this process reduces CO_(2) emission costs by 27.56%,TAC by 15.58%(to 5.123×10^(6) USD·a^(−1)),and increases ethanol purity to>99.6%,providing an effective solution for green,efficient separation.
基金Supported by Shanghai Agriculture Applied Technology Development Program (Grant No.T20220120).
文摘[Objectives]This study was conducted to establish a quantitative assessment method for the textural quality of chieh-qua fruit.[Methods]Using two modes of a texture analyzer,namely TPA(texture profile analysis)and puncture,the index data of the fruit were obtained by setting different trigger forces,deformation levels,test speeds,as well as puncture speeds and puncture depths.The data included TPA hardness,adhesiveness,springiness,cohesiveness,gumminess,chewiness,resilience,as well as skin hardness,skin toughness,flesh hardness,fracturability,and compactness.[Results]Different deformation levels had a significant impact on all parameters.Hardness,adhesiveness,gumminess and chewiness showed a trend of first increasing and then decreasing with the deformation level increasing.When the deformation level was 30%,the adhesiveness,gumminess and chewiness reached their maximum values.When the deformation level was 50%,TPA hardness reached its maximum.When the compression speed was 3 mm/s,the measured values of TPA hardness,adhesiveness,chewiness,and resilience were at their maximums.The skin hardness varied significantly under different trigger forces.When the trigger force was 15 g,the skin hardness reached a maximum value of 944.63 g,and the skin toughness,flesh hardness,fracturability,and compactness also reach their maximum values respectively.When the puncture depth was 12 mm,the flesh hardness and skin toughness reached their maximums of 682.51 g and 1.82 mm,respectively.In the TPA mode,the flesh hardness of chieh-qua showed an extremely significant negative correlation with springiness,cohesiveness,and resilience(P<0.01).The fruit fracturability detected by puncture had an extremely significant positive correlation with compactness(P<0.01).[Conclusions]The evaluation method for measuring chieh-qua texture by combining TPA and the puncture mode could accurately and quantitatively reflect the differences in the flesh texture quality of chieh-qua.The optimal parameters for texture measurement of chieh-qua fruit were determined as a 15 g trigger force with 50%deformation and a 3 mm/s compression speed in TPA mode,and a 15 g trigger force with a 12 mm puncture depth in puncture mode.Puncture speed was found to have no significant effect on the texture indices of chieh-qua.
基金supported by the National Natural Science Foundation of China(No.50778100) funded in part by Afton Chemical Corporation
文摘In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a personal exposure study was conducted for school children, and office workers in Beijing, China. For all participants （N = 114）, the mean personal 24-hr exposure concentration was 102.5, 14.7, 0.093, 0.528, 0.934, 0.174 and 0.703 μg/m 3 for PM 2.5 , black carbon, Mn, Al, Ca, Pb, and Fe. Children’s exposure concentrations of PM 2.5 were 4–5 times higher than those in related studies. The ambient concentration of PM 2.5 （128.5 μg/m 3 ） was significantly higher than the personal exposure concentration （P 0.05）, and exceed the reference concentration （25 μg/m 3 ） of WHO air quality guideline. Good correlation relationships and significant differences were identified between ambient concentration and personal exposure concentration. The relationships indicate that the ambient concentration is the main factor influencing personal exposure concentration, but is not a good indicator of personal exposure concentration. Outdoor activities （commute mode, exposure to heating, workday or weekend travel） influenced personal exposure concentrations significantly, but the magnitude of the influence from indoor activities （exposure to cooking） was masked by the high ambient concentrations.
基金jointly supported by the National Key Research and Development Program of China(2022YFC2106300)the National Nature Science Foundation of China(U2267226).
文摘This study employed the Box-Behnken design in response surface methodology(RSM)to optimize predistillation and pressurized distillation column parameters in methanol distillation.Statistical and fittinganalyses demonstrated the effects of operational parameters and their interactions on product purity and operating costs.Results showed that for methanol mass fraction in the product,the top distillate of the predistillation column(D_(1)),the interaction between D_(1) and the top distillate of the pressurized distillation column(D_(2)),and the interaction between the theoretical plates of the pressurized distillation column(N_(2))and its refluxratio(R_(2))significantlyaffected the outcome,in addition to pressurized distillation column parameters.Acetone mass fraction was mainly influencedby predistillation column parameters and their interactions,with minimal relation to the pressurized distillation column.Operating costs were primarily affected by the refluxratio(R),withdrawal(D)of both columns,and their interactions.Optimization strategies involved increasing theoretical plates and reducing refluxratios compared to the initial plan,achieving energy-saving and consumption-reduction goals.The process required the pressurized distillation column‘s methanol mass fraction to exceed 99.80%,acetone mass fraction below 2×10^(-8),and formaldehyde mass fraction below 5×10^(-9),with a feed rate of 6100 kg·h^(-1).Plans A,B,and C achieved energy-savings of 29.80%,21.78%,and 25.50%respectively,while ensuring separation efficiencyand product quality.This research provides theoretical and practical guidance for optimizing the methanol distillation process,helping to reduce energy consumption and production costs,thereby enhancing corporate competitiveness.
基金the National Key R&D Program of China(No.2017YFA0700500)the National Natural Science Foundation of China(No.62172202)+1 种基金the Experiment Project of ChinaManned Space Program(No.HYZHXM01019)the Fundamental Research Funds for the Central Universities from Southeast University(No.3207032101C3).
文摘In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.
基金Suzhou Health Committee and Science and Technology Bureau,No.KJXW2019005.
文摘BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2DM)are considered to have a predisposition to hepatic steatosis.However,the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University,who underwent MR mDIXONQuant examination to quantify the hepatic fat fraction(HFF).According to body mass index(BMI),the patients were divided into normal weight,overweight,and obese groups.The differences in general statistics,biochemical parameters,islet function,and HFF were compared among the three groups.The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.RESULTS The HFF of T2DM patients gradually increased in the normal weight,overweight,and obese groups(P<0.05).Spearman correlation analysis showed that in T2DM patients,HFF was negatively correlated with age and high-density lipoprotein cholesterol(P<0.05),whereas it was positively correlated with BMI,waist-hip ratio,fasting plasma glucose,alanine aminotransferase(ALT),aspartate aminotransferase,bilirubin,glutamyl transpeptidase,lactate dehydrogenase,albumin(ALB),uric acid(UA),total cholesterol,TG,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,free triiodothyronine,fasting insulin,fasting C-peptide,and homeostasis model assessment of insulin resistance(P<0.05).Multiple linear regression analysis showed significant positive influences of BMI,ALT,LDL-C,UA,and ALB on HFF in T2DM patients(P<0.05).Binary logistic regression analysis showed that BMI,ALT,ALB,and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients,and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times(P<0.05).CONCLUSION The HFF of T2DM patients increases with BMI.Higher BMI,ALT,ALB,and LDLC are independent risk factors for moderate to severe fatty liver in T2DM patients.
文摘BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ(AIS).METHODS This study enrolled 43 patients with T2DM combined with lung AIS(T2DM+AIS group),43 patients with T2DM alone(T2DM group),43 patients with lung AIS alone(AIS group),and 43 healthy volunteers(control group).The serum levels of vWF,insulin-like growth factor 1,and insulin-like growth factor binding protein 3 were determined.Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTS Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(P<0.05).Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group(P<0.05).There was no significant difference in serum vWF level between the T2DM and AIS groups.In the T2DM+AIS group,serum vWF was independently associated and positively correlated with serum levels of insulinlike growth factor 1 and insulin-like growth factor binding protein 3(P<0.05).CONCLUSION Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.
基金the financial support from the National Key Research and Development Program of China(2022YFA1207503)the Giga Force Electronics Interdisciplinary Funding(JJHXM002208-2023)。
文摘Exploring suitable high-capacity V_(2)O_(5)-based cathode materials is essential for the rapid advancement of aqueous zinc ion batteries(ZIBs).However,the typical problem of slow Zn^(2+)diffusion kinetics has severely limited the feasibility of such materials.In this work,unique hydrated vanadates(CaVO,BaVO)were obtained by intercalation of Ca^(2+)or Ba^(2+)into hydrated vanadium pentoxide.In the CaVO//Zn and BaVO//Zn batteries systems,the former delivered up to a 489.8 mAh g^(-1)discharge specific capacity at 0.1 A g^(-1).Moreover,the remarkable energy density of 370.07 Wh kg^(-1)and favorable cycling stability yard outperform BaVO,pure V_(2)O_(5),and many reported cathodes of similar ionic intercalation compounds.In addition,pseudocapacitance analysis,galvanostatic intermittent titration(GITT)tests,and Trasatti analysis revealed the high capacitance contribution and Zn^(2+)diffusion coefficient of CaVO,while an in-depth investigation based on EIS elucidated the reasons for the better electrochemical performance of CaVO.Notably,ex-situ XRD,XPS,and TEM tests further demonstrated the Zn^(2+)insertion/extraction and Zn-storage mechanism that occurred during the cycle in the CaVO//Zn battery system.This work provides new insights into the intercalation of similar divalent cations in vanadium oxides and offers new solutions for designing cathodes for high-capacity aqueous ZIBs.
基金Supported by the National Natural Science Foundation of China under Grant No.1143505sponsored by K.C.Wong Magna Fund in Ningbo University
文摘The(2 + 1)-dimensional Ito equation is extended to a general form including some nonintegrable effects via introducing generalized bilinear operators. It is pointed out that the nonintegrable(2 + 1)-dimensional Ito equation contains lump solutions and interaction solutions between lump and stripe solitons. The result shows that the lump soliton will be swallowed or arisen by a stripe soliton in a fixed time. Furthermore, by the interaction between a lump and a paired resonant stripe soliton, the lump will be transformed to an instanton or a rogue wave.
文摘The method of density matching between the solid and liquid phases is often adopted to effectively eliminate the effect of sedimentation of suspensions on dynamic behavior of a colloidal system. Experiments on crystallization of charged colloidal microspheres with di- ameter of 98 nm dispersed in density-matched and -unmatched media （mixtures of H20 and D20 in proper proportion） are compared to examine the influence of sedimentation. Reflection spectra of colloidal suspensions were used to monitor the crystallization process. Results showed that the crystal size of the density-unmatched （namely, in the presence of sedimentation） sample grew faster than that of the density-matched （in the absence of sedi- mentation） case at the initial stage of the crystallization, and then the latter overtook and outstripped the former. To explain these observations, we assume that in the settling of crystals sedimentation facilitates result in more particles getting into the crystal structures. However, as the crystals increase to varying sizes, the settling velocities become large and hydrodynamic friction strips off some particles from the delicate crystal structures. Overall, the sedimentation appears to accelerate the crystal size growth initially and then retard the growth. In addition, the crystal structures formed under microgravity were more closely packed than that in normal gravity.
文摘BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a lower HBV deoxyribonucleic acid(DNA)load.The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood.AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.METHODS 1603 HBsAg-seropositive patients were included in the study.We first explored the relationship between patients'lipid levels,hepatic steatosis,and HBV DNA load.Also,we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro.By knocking down and overexpressing Plin2,we observed whether Plin2 regulates autophagy and HBV replication.By inhibiting both Plin2 and cellular autophagy under high lipid stimulation,we examined whether the Plin2-autophagy pathway regulates HBV replication.RESULTS The results revealed that serum triglyceride levels,high-density lipoprotein levels,and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group.Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load.Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAgpositive and HBeAg-negative groups.An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism.The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg,HBeAg,and HBV DNA load.Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins.Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy.Knocking down Plin2 and blocking autophagy with 3-methyladenine(3-MA)inhibited HBV DNA replication.CONCLUSION In conclusion,lipid metabolism is a significant factor affecting HBV load in patients with HBV infection.The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.
基金supported by the Natural Science Foundation of China(12427811)the National Key Research and Development Program of China(2022YFA1207503)the Giga Force Electronics Interdisciplinary Funding(JJHXM002208-2023).
文摘Developing high voltage lithium cobalt oxide(LiCoO_(2),LCO)is crucial for attaining the enhanced capacity and energy density of lithium-ion batteries.However,severe interface and structural instability lead to rapid degradation of LCO under the condition of high voltage.Herein,a successful strategy for modifying the interface of LCO is developed using a one-step high temperature process.By coating LCO with Li3TiMg(PO4)3(LTMP),the obtained phosphate can stabilize the surface crystal structure and boost the mechanical stability of LCO.The high temperature process enables the successful doping of Ti/Mg into the LCO lattice,effectively inhibiting the harmful phase transition effect across various voltage ranges.Compared to commercial LCO and the reported studies,the modified LCO@LTMP performs outstanding electrochemical performance.It delivers an initial discharge specific capacity of 216.4 mAh·g^(−1) at 0.1 C and 189.98 mAh·g^(−1) at 1 C.After 250 cycles at 1 C,it preserves 87.46%of its initial capacity,manifesting excellent cycling stability.Moreover,it provides a discharge specific capacity of 115.9 mAh·g^(−1) at 5 C,demonstrating outstanding rate performance.This work holds great potential for practical applications and offers valuable guidance for developing other high performance cathode materials in rechargeable batteries.
基金the conservation management and soil erosion project funded by the Yangling Vocational&Technical College,grant number:A2019009Jinshi Jian was supported by the Strategic Priority Research Program of Chinese Academy of Sci-ences,under contract number XDA20040202+3 种基金the US Depart-ment of Energy,Office of Science,Biological and Environmental Research as part of the Terrestrial Ecosystem Sciences Program,under contract DE-AC05-76RL01830Can Du was supported by the Yangling Vocational&Technical College 2019 Natural Science Research Fund Project,under grant number:A2019048Ryan Stewart was supported by the U.S.Department of Agriculture NRCS Conservation Innovation Grant(No.69-3A75-14-260)the Vir-ginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture,U.S.Department of Agriculture.
文摘Conservation management practices e including agroforestry,cover cropping,no-till,reduced tillage,and residue return e have been applied for decades to control surface runoff and soil erosion,yet results have not been integrated and evaluated across cropping systems.In this study we collected data comparing agricultural production with and without conservation management strategies.We used a bootstrap resampling analysis to explore interactions between practice type,soil texture,surface runoff,and soil erosion.We then used a correlation analysis to relate changes in surface runoff and soil erosion to 13 other soil health and agronomic indicators,including soil organic carbon,soil aggregation,infil-tration,porosity,subsurface leaching,and cash crop yield.Across all conservation management practices,surface runoff and erosion had respective mean decreases of 67%and 80%compared with controls.Use of cover cropping provided the largest decreases in erosion and surface runoff,thus emphasizing the importance of maintaining continuous vegetative cover on soils.Coarse-and medium-textured soils had greater decreases in both erosion and runoff than fine-textured soils.Changes in surface runoff and soil erosion under conservation management were highly correlated with soil organic carbon,aggregation,porosity,infiltration,leaching,and yield,showing that conservation practices help drive important in-teractions between these different facets of soil health.This study offers the first large-scale comparison of how different conservation agriculture practices reduce surface runoff and soil erosion,and at the same time provides new insight into how these interactions influence the improvement or loss of soil health。
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB11040500) to Hui-Shan GuoNational Natural Science Foundation(31500119) to Chenlei HuaNational Natural Science Foundation(31600124) to Jian-Hua Zhao
文摘Verticillium wilt disease becomes a major threat to many economically important crops. It is unclear whether and how plant immunity takes place during cotton-Verticillium interaction due to the lack of marker genes. Taking advantage of cotton （Gossypium hirsutum） genome, we discovered pathogenesis-related （PR） gene families, which have been widely used as markers of immune responses in plants. To profile the expression of G. hirsutum PR genes in the process of plant immunity, we treated cotton roots with two immunogenic peptides, fig22 and nlp20 known as pathogen-associated molecular patterns, as well as three Verticillium dahliae-derived peptides, nlp20vd2, nlp23vd3, and nlp23vd4 which are highly identical to nlp20. Quantitative real-time PCR results revealed that 14 G. hirsutum PR gene （GhPR） families were induced or suppressed independently in response to fig22, nip20, nlp20va2, nlp23vd3, and nlp23vd4. Most GhPR genes are expressed highest at 3 h post incubation of immunogenic peptides. Compared to fig22 and nlp20, nlp20vd2 is more effective to trigger up-regulated expression of GhPR genes. Notably, both nlp23vd3 and nlp23vd4 are able to induce GhPR gene up-regulation, although they do not induce necrosis on cotton leaves. Thus, our results provide marker genes and new immunogenic peptides for further investigation of cotton-V, dahliae interaction.
基金supported by National Natural Science Foundation of China(31770782)the Ministry of Science and Technology of China(2016YFA0503200)+1 种基金the Shenzhen Science and Technology Program(JCYJ20200109110403829 and KQTD20190929173906742)Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes(2019KSYS006)to J.D.
文摘RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2(SHH2) is an H3 K9 me1 reader. Our structural studies reveal that H3 K9 me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di-and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a monomethyllysine recognition mechanism which potentially links RdDM to H3 K9 me1 in maize.
基金the Chinese Academy of Sciences and the National Natural Science Foundation of China(31970580)to M.L.the National Key R&D Program(2016YFA0503200)+1 种基金Shenzhen Science and Technology Program(JCYJ20200109110403829 and KQTD20190929173906742)Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes(2019KSYS006)to J.D.
文摘DNA methylation,a conserved epigenetic mark,is critical for tuning temporal and spatial gene expression.The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1(ROS1)initiates active DNA demethylation and is required to prevent DNA hypermethylation at thousands of genomic loci.However,how ROS1 is recruited to specific loci is not well understood.Here,we report the discovery of Arabidopsis AGENET Domain Containing Protein 3(AGDP3)as a cellular factor that is required to prevent gene silencing and DNA hypermethylation.AGDP3 binds to H3K9me2 marks in its target DNA via its AGD12 cassette.Analysis of the crystal structure of the AGD12 cassette of AGDP3 in complex with an H3K9me2 peptide revealed that dimethylated H3 K9 and unmodified H3 K4 are specifically anchored into two different surface pockets.A histidine residue located in the methyllysine binding aromatic cage provides AGDP3 with pH-dependent H3K9me2 binding capacity.Our results uncover a molecular mechanism for the regulation of DNA demethylation by the gene silencing mark H3K9me2.
