Electrochemical reduction of carbon dioxide(CO_(2)RR)is a promising approach to complete the carbon cycle and potentially convert CO_(2)into valuable chemicals and fuels.Cu is unique among transition metals in its abi...Electrochemical reduction of carbon dioxide(CO_(2)RR)is a promising approach to complete the carbon cycle and potentially convert CO_(2)into valuable chemicals and fuels.Cu is unique among transition metals in its ability to catalyze the CO_(2)RR and produce multi-carbon products.However,achieving high selectivity for C2+products is challenging for copper-based catalysts,as C–C coupling reactions proceed slowly.Herein,a surface modification strategy involving grafting long alkyl chains onto copper nanowires(Cu NWs)has been proposed to regulate the electronic structure of Cu surface,which facilitates*CO-*CO coupling in the CO_(2)RR.The hydrophobicity of the catalysts increases greatly after the introduction of long alkyl chains,therefore the hydrogen evolution reaction(HER)has been inhibited effectively.Such surface modification approach proves to be highly efficient and universal,with the Faradaic efficiency(FE)of C_(2)H_(4) up to 53%for the optimized Cu–SH catalyst,representing a significant enhancement compared to the pristine Cu NWs(30%).In-situ characterizations and theoretical calculations demonstrate that the different terminal groups of the grafted octadecyl chains can effectively regulate the charge density of Cu NWs interface and change the adsorption configuration of*CO intermediate.The top-adsorbed*CO intermediates(*COtop)on Cu–SH catalytic interface endow Cu–SH with the highest charge density,which effectively lowers the reaction energy barrier for*CO-*CO coupling,promoting the formation of the*OCCO intermediate,thereby enhancing the selectivity towards C_(2)H_(4).This study provides a promising method for designing efficient Cu-based catalysts with high catalytic activity and selectivity towards C2H4.展开更多
Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels r...Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.展开更多
Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate ...Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.展开更多
This paper considers the problem of target and jamming recognition for the pulse Doppler radar fuze(PDRF).To solve the problem,the matched filter outputs of the PDRF under the action of target and jamming are analyzed...This paper considers the problem of target and jamming recognition for the pulse Doppler radar fuze(PDRF).To solve the problem,the matched filter outputs of the PDRF under the action of target and jamming are analyzed.Then,the frequency entropy and peak-to-peak ratio are extracted from the matched filter output of the PDRF,and the time-frequency joint feature is constructed.Based on the time-frequency joint feature,the naive Bayesian classifier(NBC)with minimal risk is established for target and jamming recognition.To improve the adaptability of the proposed method in complex environments,an online update process that adaptively modifies the classifier in the duration of the work of the PDRF is proposed.The experiments show that the PDRF can maintain high recognition accuracy when the signal-to-noise ratio(SNR)decreases and the jamming-to-signal ratio(JSR)increases.Moreover,the applicable analysis shows that he ONBCMR method has low computational complexity and can fully meet the real-time requirements of PDRF.展开更多
While encryption technology safeguards the security of network communications,malicious traffic also uses encryption protocols to obscure its malicious behavior.To address the issues of traditional machine learning me...While encryption technology safeguards the security of network communications,malicious traffic also uses encryption protocols to obscure its malicious behavior.To address the issues of traditional machine learning methods relying on expert experience and the insufficient representation capabilities of existing deep learning methods for encrypted malicious traffic,we propose an encrypted malicious traffic classification method that integrates global semantic features with local spatiotemporal features,called BERT-based Spatio-Temporal Features Network(BSTFNet).At the packet-level granularity,the model captures the global semantic features of packets through the attention mechanism of the Bidirectional Encoder Representations from Transformers(BERT)model.At the byte-level granularity,we initially employ the Bidirectional Gated Recurrent Unit(BiGRU)model to extract temporal features from bytes,followed by the utilization of the Text Convolutional Neural Network(TextCNN)model with multi-sized convolution kernels to extract local multi-receptive field spatial features.The fusion of features from both granularities serves as the ultimate multidimensional representation of malicious traffic.Our approach achieves accuracy and F1-score of 99.39%and 99.40%,respectively,on the publicly available USTC-TFC2016 dataset,and effectively reduces sample confusion within the Neris and Virut categories.The experimental results demonstrate that our method has outstanding representation and classification capabilities for encrypted malicious traffic.展开更多
Introduction:This study aimed to establish an animal model of open abdomen(OA)through temporary abdominal closure via different techniques.Methods:Adult male Sprague-Dawley rats were randomly divided into three groups...Introduction:This study aimed to establish an animal model of open abdomen(OA)through temporary abdominal closure via different techniques.Methods:Adult male Sprague-Dawley rats were randomly divided into three groups:group A(OA with polypropylene mesh alone);group B(OA with polypro-pylene mesh combined with a patch);and group C(OA with polypropylene mesh and a sutured patch).Vital signs,pathophysiological changes,and survival rates were closely monitored in the rats for 7 days after surgery.Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing.Results:The results showed no significant difference in mortality rates among the three groups(p>0.05).However,rats in group B exhibited superior overall condi-tion,cleaner wounds,and a higher rate of wound healing compared to the other groups(p<0.05).Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups.Histopathological examinations revealed fibrous hyperpla-sia,inflammatory cell infiltration,neovascularization,and collagen deposition in all groups.Group B demonstrated enhanced granulation tissue generation,neovasculari-zation,and collagen deposition compared to the other groups(p<0.05).Conclusions:Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA.This model successfully replicated the patho-logical and physiological changes in postoperative patients with OA,specifically the progress of abdominal skin wound healing.It provides a practical and reliable animal model for OA research.展开更多
Purpose–This study aims to enhance the accuracy of key entity extraction from railway accident report texts and address challenges such as complex domain-specific semantics,data sparsity and strong inter-sentence sem...Purpose–This study aims to enhance the accuracy of key entity extraction from railway accident report texts and address challenges such as complex domain-specific semantics,data sparsity and strong inter-sentence semantic dependencies.A robust entity extraction method tailored for accident texts is proposed.Design/methodology/approach–This method is implemented through a dual-branch multi-task mutual learning model named R-MLP,which jointly performs entity recognition and accident phase classification.The model leverages a shared BERT encoder to extract contextual features and incorporates a sentence span indexing module to align feature granularity.A cross-task mutual learning mechanism is also introduced to strengthen semantic representation.Findings–R-MLP effectively mitigates the impact of semantic complexity and data sparsity in domain entities and enhances the model’s ability to capture inter-sentence semantic dependencies.Experimental results show that R-MLP achieves a maximum F1-score of 0.736 in extracting six types of key railway accident entities,significantly outperforming baseline models such as RoBERTa and MacBERT.Originality/value–This demonstrates the proposed method’s superior generalization and accuracy in domainspecific entity extraction tasks,confirming its effectiveness and practical value.展开更多
The group Ⅳ–Ⅵ semiconductor,SnSe,is abundant on the earth and is a promising thermoelectric(TE)material due to its low thermal conductivity.However,the p-type SnSe polycrystals have low electrical conductivities du...The group Ⅳ–Ⅵ semiconductor,SnSe,is abundant on the earth and is a promising thermoelectric(TE)material due to its low thermal conductivity.However,the p-type SnSe polycrystals have low electrical conductivities due to their low carrier concentration,significantly limiting their further applications.This study introduced the argyrodite-type Ag_(9)GaSe_(6) compound into the SnSe matrix to effectively increase the hole carrier concentration,increasing the electrical conductivity.A high electrical conductivity of 50.5 S cm^(−1) was obtained for the SnSe+0.5 wt%Ag_(9)GaSe_(6) sample at 323 K.Due to the increased electrical conductivity,the SnSe+0.5 wt%Ag_(9)GaSe_(6) sample had an average power factor(PFave)value of~410μW m^(-1) K^(-2) in the 323–823 K temperature range,a nearly four times enhancement compared to the undoped SnSe sample.Additionally,the thermal conductivity slightly increased due to the introduction of the Ag_(9)GaSe_(6) compound.However,the electrical transport properties were significantly enhanced,making up for the improvement in thermal conductivity.Consequently,the SnSe+0.5 wt%Ag_(9)GaSe_(6) sample obtained a peak thermoelectric figure of merit ZT value of~1.2 at 823 K and a ZT_(ave) value of 0.58 in the 323–823 K temperature range.The proposed strategy improved the ZT and ZT_(ave) values of SnSe-based TE materials at room temperature and provided a systematic strategy for modifying SnSe-based TE materials.Moreover,the thermoelectric properties of SnSe can be effectively improved by introducing the Ag_(9)GaSe_(6) compound for doping,and waste heat power generation can be effectively carried out in the middle temperature region.展开更多
Direct alcohol fuel cells(DAFCs)are powered by the alcohol electro-oxidation reaction(AOR),where an electrocatalyst with an optimal electronic structure can accelerate the sluggish AOR.Interestingly,strain engineering...Direct alcohol fuel cells(DAFCs)are powered by the alcohol electro-oxidation reaction(AOR),where an electrocatalyst with an optimal electronic structure can accelerate the sluggish AOR.Interestingly,strain engineering in hetero-catalysis offers a promising route to boost their catalytic activity.Herein,we report on a class of monodispersed ultrathin twisty PdBi alloy nanowires(TNWs)assemblies with face-centered structures that drive AORs.These thin nanowire structures expose a large number of reactive sites.Strikingly,Pd_(6)Bi_(1)TNWs show an excellent current density of 2066,3047,and 1231 mA mg_(Pd)^(-1)for oxidation of ethanol,ethylene glycol,and glycerol,respectively.The“volcano-like”behaviors observed on PdBi TNWs for AORs indicate that the maximum catalytic mass activity is a well balance between active intermediates and blocking species at the interface.This study offers an effective and universal method to build novel nanocatalysts in various applications by rationally designing highly efficient catalysts with specific strain.展开更多
Conventional parameter estimation methods for pseudo-random binary code-linear frequency modulation(PRBC-LFM)signals require prior knowledge,are computationally complex,and exhibit poor performance at low signal-to-no...Conventional parameter estimation methods for pseudo-random binary code-linear frequency modulation(PRBC-LFM)signals require prior knowledge,are computationally complex,and exhibit poor performance at low signal-to-noise ratios(SNRs).To overcome these problems,a blind parameter estimation method based on a Duffing oscillator array is proposed.A new relationship formula among the state of the Duffing oscillator,the pseudo-random sequence of the PRBC-LFM signal,and the frequency difference between the PRBC-LFM signal and the periodic driving force signal of the Duffing oscillator is derived,providing the theoretical basis for blind parameter estimation.Methods based on amplitude method,short-time Fourier transform method,and power spectrum entropy method are used to binarize the output of the Duffing oscillator array,and their performance is compared.The pseudo-random sequence is estimated using Duffing oscillator array synchronization,and the carrier frequency parameters are obtained by the relational expressions and characteristics of the difference frequency.Simulation results show that this blind estimation method overcomes limitations in prior knowledge and maintains good parameter estimation performance up to an SNR of-35 dB.展开更多
Osteosarcoma(OS)is a primary high-grade malignant bone neoplasm,and the prognosis ofOS remains poor due to early metastasis.Leptin plays an essential role in tumorigenesis,but the role of leptin in the development of ...Osteosarcoma(OS)is a primary high-grade malignant bone neoplasm,and the prognosis ofOS remains poor due to early metastasis.Leptin plays an essential role in tumorigenesis,but the role of leptin in the development of OS is still not fully understood.In this study,we used a human osteosarcomaMG-63 cell line as an experimentalmodel.MG-63 cells were treated with leptin,and cell proliferation,apoptosis,adhesion,invasion,and gene expression,were evaluated.The results showed that leptin promoted proliferation,decreased adhesion,suppressed apoptosis,and promoted invasion,of MG-63 cells.Moreover,the expression of SIRT1 was upregulated in MG-63 cells exposed to leptin.Furthermore,MMP-2,8,and 9 were significantly upregulated by SIRT1,while SIRT1 knockdown inhibited the proliferation and invasion of MG-63 cells.In conclusion,our results suggest that leptin promotes OS cell proliferation and invasion by inducing the expression of SIRT1.展开更多
The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take ...The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take advantage of these developments.Here we consider the case of many vehicles forming a queue,i.e.,vehicles traveling at a predetermined speed and distance apart.While the majority of existing studies on this subject have focused on the influence of the longitudinal vehicle spacing,vehicle speed,and the number of vehicles on aerodynamic drag and fuel economy,this study considers the lateral offset distance of the vehicle queue.The group fuel consumption savings rate is calculated and analyzed.As also demonstrated by experimental results,some aerodynamic benefits exist.Moreover,the fuel consumption saving rate of the vehicle queue decreases as the lateral offset distance increases.展开更多
Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hyp...Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hypertrophy and systemic metabolism.We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy,improves metabolic performance,and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT,offering potential therapeutic strategies for metabolic syndromes.Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis,Bambi gene is shown to be a direct target of HIF2α,which is further confirmed by ChIP-qPCR and promoter luciferase assay.Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters,even under high-fat diet conditions.This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs)into thermogenic adipocytes,contributing to systemic metabolic improvements,potentially through the secretory factor.Notably,mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders,highlighting a potential therapeutic pathway for metabolic syndrome management.Thus,skeletal muscle-specific deletion of Bambi triggers muscle growth,enhances metabolic performance,and activates thermogenic adipocytes.These findings suggest Bambi as a novel therapeutic target for metabolic syndromes,providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement.The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism,offering a novel perspective on treating metabolic disorders.展开更多
目的:评价肿瘤电场治疗仪用于治疗复发胶质母细胞瘤患者的初步安全性和有效性。方法:选取2020年4月至2020年8月期间中南大学湘雅医院和解放军总医院6例受试者,均为男性,中位年龄53(48~68)岁。入组复发胶质母细胞瘤受试者并收集临床资料...目的:评价肿瘤电场治疗仪用于治疗复发胶质母细胞瘤患者的初步安全性和有效性。方法:选取2020年4月至2020年8月期间中南大学湘雅医院和解放军总医院6例受试者,均为男性,中位年龄53(48~68)岁。入组复发胶质母细胞瘤受试者并收集临床资料,通过观察受试者治疗期间不良事件的发生率、肿瘤进展时间(time to progression,TTP)和总生存时间(overall survival,OS)评估治疗的安全性和有效性。结果:入组6例受试者中位随访时间10.9(8.4~22.7)个月,所有受试者发生肿瘤进展,5例随访至死亡,截至随访截止1例生存。中位肿瘤进展时间(median time to progression,m TTP)为4.7个月(95%CI:3.62~5.78),中位无进展生存时间(median progression-free survival,mPFS)为4.7个月(95%CI:3.62~5.78),中位总生存时间(median overall survival,mOS)为10.9个月(95%CI:8.86~12.94)。客观缓解率(CR+PR)33.3%;疾病控制率(SD+PR+CR)83.3%。治疗相关的不良事件主要为头皮皮疹,发生率为66.7%,经调整电极片黏贴位置、保持创口干燥、涂抹类固醇类软膏或抗生素软膏后均可有效缓解。结论:肿瘤电场治疗仪用于治疗复发胶质母细胞瘤的受试者在电场治疗过程中呈现良好的初步安全性和有效性。展开更多
Generating B cell-deficient mutant is the first step to produce human antibody repertoires in large animal models. In this study, we applied the clustered regularly interspaced short palindromic repeat （CRISPR）/CRIS...Generating B cell-deficient mutant is the first step to produce human antibody repertoires in large animal models. In this study, we applied the clustered regularly interspaced short palindromic repeat （CRISPR）/CRISPR-associated （Cas） system to target the JH region of the pig IgM heavy chain gene which is crucial for B cell development and differentiation. Transfection of IgM-targeting Cas9 plasmid in primary porcine fetal fibroblasts （PFFs） enabled inducing gene knock out （KO） in up to 53.3% of colonies analyzed, a quarter of which harbored biallelic modification, which was much higher than that of the traditional homologous recombination （HR）. With the aid of somatic cell nuclear transfer （SCNT） technology, three piglets with the biallelic lgM heavy chain gene mutation were produced. The piglets showed no antibody-producing B cells which indicated that the biallelic mutation of the lgM heavy chain gene effectively knocked out the function of the IgM and resulted in a B cell-deficient phenotype. Our study suggests that the CRISPR/Cas9 system combined with SCNT technology is an efficient genome-editing approach in pigs.展开更多
Unbalanced brain serotonin(5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydr...Unbalanced brain serotonin(5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2(TPH2). In the present study, the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer(SCNT) and 10 Tph2 targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth.However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced behavior abnomality.展开更多
Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylationstate-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were...Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylationstate-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3Kgme2 and H3K27me2 interact with ceKDMTA in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specifieity of ceDKM7A for both H3K9me2 and H3K27me2.展开更多
文摘Electrochemical reduction of carbon dioxide(CO_(2)RR)is a promising approach to complete the carbon cycle and potentially convert CO_(2)into valuable chemicals and fuels.Cu is unique among transition metals in its ability to catalyze the CO_(2)RR and produce multi-carbon products.However,achieving high selectivity for C2+products is challenging for copper-based catalysts,as C–C coupling reactions proceed slowly.Herein,a surface modification strategy involving grafting long alkyl chains onto copper nanowires(Cu NWs)has been proposed to regulate the electronic structure of Cu surface,which facilitates*CO-*CO coupling in the CO_(2)RR.The hydrophobicity of the catalysts increases greatly after the introduction of long alkyl chains,therefore the hydrogen evolution reaction(HER)has been inhibited effectively.Such surface modification approach proves to be highly efficient and universal,with the Faradaic efficiency(FE)of C_(2)H_(4) up to 53%for the optimized Cu–SH catalyst,representing a significant enhancement compared to the pristine Cu NWs(30%).In-situ characterizations and theoretical calculations demonstrate that the different terminal groups of the grafted octadecyl chains can effectively regulate the charge density of Cu NWs interface and change the adsorption configuration of*CO intermediate.The top-adsorbed*CO intermediates(*COtop)on Cu–SH catalytic interface endow Cu–SH with the highest charge density,which effectively lowers the reaction energy barrier for*CO-*CO coupling,promoting the formation of the*OCCO intermediate,thereby enhancing the selectivity towards C_(2)H_(4).This study provides a promising method for designing efficient Cu-based catalysts with high catalytic activity and selectivity towards C2H4.
基金supported by the National Natural Science Foundation of China,No.81571046(to KZ)Key Project of Educational Department of Liaoning Province,No.LJKZ0755(to KZ)+2 种基金Project of Department of Science&Technology of Liaoning Province,No.2023JH2/20200116(to KZ)Shenyang Young and Middleaged Innovative Talents Support Program,No.RC210240(to KZ)the 345 Talent Project of Shengjing Hospital of China Medical University(to LH)。
文摘Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.
基金supported by the project of Central Funds Guiding the Local Science and Technology Development(No.20212ZDD02010)。
文摘Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
基金supported by the National Natural Science Foundation of China(Grant No.61973037 and No.61673066).
文摘This paper considers the problem of target and jamming recognition for the pulse Doppler radar fuze(PDRF).To solve the problem,the matched filter outputs of the PDRF under the action of target and jamming are analyzed.Then,the frequency entropy and peak-to-peak ratio are extracted from the matched filter output of the PDRF,and the time-frequency joint feature is constructed.Based on the time-frequency joint feature,the naive Bayesian classifier(NBC)with minimal risk is established for target and jamming recognition.To improve the adaptability of the proposed method in complex environments,an online update process that adaptively modifies the classifier in the duration of the work of the PDRF is proposed.The experiments show that the PDRF can maintain high recognition accuracy when the signal-to-noise ratio(SNR)decreases and the jamming-to-signal ratio(JSR)increases.Moreover,the applicable analysis shows that he ONBCMR method has low computational complexity and can fully meet the real-time requirements of PDRF.
基金This research was funded by National Natural Science Foundation of China under Grant No.61806171Sichuan University of Science&Engineering Talent Project under Grant No.2021RC15+2 种基金Open Fund Project of Key Laboratory for Non-Destructive Testing and Engineering Computer of Sichuan Province Universities on Bridge Inspection and Engineering under Grant No.2022QYJ06Sichuan University of Science&Engineering Graduate Student Innovation Fund under Grant No.Y2023115The Scientific Research and Innovation Team Program of Sichuan University of Science and Technology under Grant No.SUSE652A006.
文摘While encryption technology safeguards the security of network communications,malicious traffic also uses encryption protocols to obscure its malicious behavior.To address the issues of traditional machine learning methods relying on expert experience and the insufficient representation capabilities of existing deep learning methods for encrypted malicious traffic,we propose an encrypted malicious traffic classification method that integrates global semantic features with local spatiotemporal features,called BERT-based Spatio-Temporal Features Network(BSTFNet).At the packet-level granularity,the model captures the global semantic features of packets through the attention mechanism of the Bidirectional Encoder Representations from Transformers(BERT)model.At the byte-level granularity,we initially employ the Bidirectional Gated Recurrent Unit(BiGRU)model to extract temporal features from bytes,followed by the utilization of the Text Convolutional Neural Network(TextCNN)model with multi-sized convolution kernels to extract local multi-receptive field spatial features.The fusion of features from both granularities serves as the ultimate multidimensional representation of malicious traffic.Our approach achieves accuracy and F1-score of 99.39%and 99.40%,respectively,on the publicly available USTC-TFC2016 dataset,and effectively reduces sample confusion within the Neris and Virut categories.The experimental results demonstrate that our method has outstanding representation and classification capabilities for encrypted malicious traffic.
基金Postgraduate Research&Practice Innovation Program of Jiangsu Province,Grant/Award Number:SJCX23_0092National Natural Science Foundation of China,Grant/Award Number:82270595Jiangsu Provincial Medical Innovation Center,Grant/Award Number:CXZX202217。
文摘Introduction:This study aimed to establish an animal model of open abdomen(OA)through temporary abdominal closure via different techniques.Methods:Adult male Sprague-Dawley rats were randomly divided into three groups:group A(OA with polypropylene mesh alone);group B(OA with polypro-pylene mesh combined with a patch);and group C(OA with polypropylene mesh and a sutured patch).Vital signs,pathophysiological changes,and survival rates were closely monitored in the rats for 7 days after surgery.Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing.Results:The results showed no significant difference in mortality rates among the three groups(p>0.05).However,rats in group B exhibited superior overall condi-tion,cleaner wounds,and a higher rate of wound healing compared to the other groups(p<0.05).Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups.Histopathological examinations revealed fibrous hyperpla-sia,inflammatory cell infiltration,neovascularization,and collagen deposition in all groups.Group B demonstrated enhanced granulation tissue generation,neovasculari-zation,and collagen deposition compared to the other groups(p<0.05).Conclusions:Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA.This model successfully replicated the patho-logical and physiological changes in postoperative patients with OA,specifically the progress of abdominal skin wound healing.It provides a practical and reliable animal model for OA research.
基金funded by the Technology Research and Development Plan Program of China State Railway Group Co.,Ltd.(No.Q2024T001)the Foundation of China Academy of Railway Sciences Co.,Ltd.(No:2024YJ259).
文摘Purpose–This study aims to enhance the accuracy of key entity extraction from railway accident report texts and address challenges such as complex domain-specific semantics,data sparsity and strong inter-sentence semantic dependencies.A robust entity extraction method tailored for accident texts is proposed.Design/methodology/approach–This method is implemented through a dual-branch multi-task mutual learning model named R-MLP,which jointly performs entity recognition and accident phase classification.The model leverages a shared BERT encoder to extract contextual features and incorporates a sentence span indexing module to align feature granularity.A cross-task mutual learning mechanism is also introduced to strengthen semantic representation.Findings–R-MLP effectively mitigates the impact of semantic complexity and data sparsity in domain entities and enhances the model’s ability to capture inter-sentence semantic dependencies.Experimental results show that R-MLP achieves a maximum F1-score of 0.736 in extracting six types of key railway accident entities,significantly outperforming baseline models such as RoBERTa and MacBERT.Originality/value–This demonstrates the proposed method’s superior generalization and accuracy in domainspecific entity extraction tasks,confirming its effectiveness and practical value.
基金supported by the Outstanding Youth Fund of Yunnan Province(Grant No.202201AV070005)the National Natural Science Foundation of China(Grant No.52162029)+1 种基金the National Key R&D Program of China(Grant No.2022YFF0503804)the Yunnan Science and Technology Program(202401AT070403).
文摘The group Ⅳ–Ⅵ semiconductor,SnSe,is abundant on the earth and is a promising thermoelectric(TE)material due to its low thermal conductivity.However,the p-type SnSe polycrystals have low electrical conductivities due to their low carrier concentration,significantly limiting their further applications.This study introduced the argyrodite-type Ag_(9)GaSe_(6) compound into the SnSe matrix to effectively increase the hole carrier concentration,increasing the electrical conductivity.A high electrical conductivity of 50.5 S cm^(−1) was obtained for the SnSe+0.5 wt%Ag_(9)GaSe_(6) sample at 323 K.Due to the increased electrical conductivity,the SnSe+0.5 wt%Ag_(9)GaSe_(6) sample had an average power factor(PFave)value of~410μW m^(-1) K^(-2) in the 323–823 K temperature range,a nearly four times enhancement compared to the undoped SnSe sample.Additionally,the thermal conductivity slightly increased due to the introduction of the Ag_(9)GaSe_(6) compound.However,the electrical transport properties were significantly enhanced,making up for the improvement in thermal conductivity.Consequently,the SnSe+0.5 wt%Ag_(9)GaSe_(6) sample obtained a peak thermoelectric figure of merit ZT value of~1.2 at 823 K and a ZT_(ave) value of 0.58 in the 323–823 K temperature range.The proposed strategy improved the ZT and ZT_(ave) values of SnSe-based TE materials at room temperature and provided a systematic strategy for modifying SnSe-based TE materials.Moreover,the thermoelectric properties of SnSe can be effectively improved by introducing the Ag_(9)GaSe_(6) compound for doping,and waste heat power generation can be effectively carried out in the middle temperature region.
基金supported by the National Natural Science Foundation of China(22172084 and 21773133)the World-Class Discipline Program of Shandong Province,China。
文摘Direct alcohol fuel cells(DAFCs)are powered by the alcohol electro-oxidation reaction(AOR),where an electrocatalyst with an optimal electronic structure can accelerate the sluggish AOR.Interestingly,strain engineering in hetero-catalysis offers a promising route to boost their catalytic activity.Herein,we report on a class of monodispersed ultrathin twisty PdBi alloy nanowires(TNWs)assemblies with face-centered structures that drive AORs.These thin nanowire structures expose a large number of reactive sites.Strikingly,Pd_(6)Bi_(1)TNWs show an excellent current density of 2066,3047,and 1231 mA mg_(Pd)^(-1)for oxidation of ethanol,ethylene glycol,and glycerol,respectively.The“volcano-like”behaviors observed on PdBi TNWs for AORs indicate that the maximum catalytic mass activity is a well balance between active intermediates and blocking species at the interface.This study offers an effective and universal method to build novel nanocatalysts in various applications by rationally designing highly efficient catalysts with specific strain.
基金the National Natural Science Foundation of China(Grant Nos.61973037 and 61673066).
文摘Conventional parameter estimation methods for pseudo-random binary code-linear frequency modulation(PRBC-LFM)signals require prior knowledge,are computationally complex,and exhibit poor performance at low signal-to-noise ratios(SNRs).To overcome these problems,a blind parameter estimation method based on a Duffing oscillator array is proposed.A new relationship formula among the state of the Duffing oscillator,the pseudo-random sequence of the PRBC-LFM signal,and the frequency difference between the PRBC-LFM signal and the periodic driving force signal of the Duffing oscillator is derived,providing the theoretical basis for blind parameter estimation.Methods based on amplitude method,short-time Fourier transform method,and power spectrum entropy method are used to binarize the output of the Duffing oscillator array,and their performance is compared.The pseudo-random sequence is estimated using Duffing oscillator array synchronization,and the carrier frequency parameters are obtained by the relational expressions and characteristics of the difference frequency.Simulation results show that this blind estimation method overcomes limitations in prior knowledge and maintains good parameter estimation performance up to an SNR of-35 dB.
基金the lab members for helpful discussion.This work was supported by the Key Project of Medical-Science Research of Hebei Province[20180564]the Project of the Natural Science Foundation of Hebei Province[H2019206309].
文摘Osteosarcoma(OS)is a primary high-grade malignant bone neoplasm,and the prognosis ofOS remains poor due to early metastasis.Leptin plays an essential role in tumorigenesis,but the role of leptin in the development of OS is still not fully understood.In this study,we used a human osteosarcomaMG-63 cell line as an experimentalmodel.MG-63 cells were treated with leptin,and cell proliferation,apoptosis,adhesion,invasion,and gene expression,were evaluated.The results showed that leptin promoted proliferation,decreased adhesion,suppressed apoptosis,and promoted invasion,of MG-63 cells.Moreover,the expression of SIRT1 was upregulated in MG-63 cells exposed to leptin.Furthermore,MMP-2,8,and 9 were significantly upregulated by SIRT1,while SIRT1 knockdown inhibited the proliferation and invasion of MG-63 cells.In conclusion,our results suggest that leptin promotes OS cell proliferation and invasion by inducing the expression of SIRT1.
基金This study was financially supported by the National Natural Science Foundation of China(52072156)the Postdoctoral Foundation of China(2020M682269).
文摘The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take advantage of these developments.Here we consider the case of many vehicles forming a queue,i.e.,vehicles traveling at a predetermined speed and distance apart.While the majority of existing studies on this subject have focused on the influence of the longitudinal vehicle spacing,vehicle speed,and the number of vehicles on aerodynamic drag and fuel economy,this study considers the lateral offset distance of the vehicle queue.The group fuel consumption savings rate is calculated and analyzed.As also demonstrated by experimental results,some aerodynamic benefits exist.Moreover,the fuel consumption saving rate of the vehicle queue decreases as the lateral offset distance increases.
基金supported by National Natural Science Foundation of China(82072436)Guangdong Basic and Applied Basic Research Foundation(2020B1515020046)‘GDAS’Project of Science and Technology Development(2021GDASYL-20210102003,2018GDASCX-0102)。
文摘Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hypertrophy and systemic metabolism.We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy,improves metabolic performance,and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT,offering potential therapeutic strategies for metabolic syndromes.Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis,Bambi gene is shown to be a direct target of HIF2α,which is further confirmed by ChIP-qPCR and promoter luciferase assay.Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters,even under high-fat diet conditions.This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs)into thermogenic adipocytes,contributing to systemic metabolic improvements,potentially through the secretory factor.Notably,mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders,highlighting a potential therapeutic pathway for metabolic syndrome management.Thus,skeletal muscle-specific deletion of Bambi triggers muscle growth,enhances metabolic performance,and activates thermogenic adipocytes.These findings suggest Bambi as a novel therapeutic target for metabolic syndromes,providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement.The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism,offering a novel perspective on treating metabolic disorders.
文摘目的:评价肿瘤电场治疗仪用于治疗复发胶质母细胞瘤患者的初步安全性和有效性。方法:选取2020年4月至2020年8月期间中南大学湘雅医院和解放军总医院6例受试者,均为男性,中位年龄53(48~68)岁。入组复发胶质母细胞瘤受试者并收集临床资料,通过观察受试者治疗期间不良事件的发生率、肿瘤进展时间(time to progression,TTP)和总生存时间(overall survival,OS)评估治疗的安全性和有效性。结果:入组6例受试者中位随访时间10.9(8.4~22.7)个月,所有受试者发生肿瘤进展,5例随访至死亡,截至随访截止1例生存。中位肿瘤进展时间(median time to progression,m TTP)为4.7个月(95%CI:3.62~5.78),中位无进展生存时间(median progression-free survival,mPFS)为4.7个月(95%CI:3.62~5.78),中位总生存时间(median overall survival,mOS)为10.9个月(95%CI:8.86~12.94)。客观缓解率(CR+PR)33.3%;疾病控制率(SD+PR+CR)83.3%。治疗相关的不良事件主要为头皮皮疹,发生率为66.7%,经调整电极片黏贴位置、保持创口干燥、涂抹类固醇类软膏或抗生素软膏后均可有效缓解。结论:肿瘤电场治疗仪用于治疗复发胶质母细胞瘤的受试者在电场治疗过程中呈现良好的初步安全性和有效性。
基金supported by a grant from the Jiangsu Key Laboratory of Xenotransplantation (BM2012116)
文摘Generating B cell-deficient mutant is the first step to produce human antibody repertoires in large animal models. In this study, we applied the clustered regularly interspaced short palindromic repeat （CRISPR）/CRISPR-associated （Cas） system to target the JH region of the pig IgM heavy chain gene which is crucial for B cell development and differentiation. Transfection of IgM-targeting Cas9 plasmid in primary porcine fetal fibroblasts （PFFs） enabled inducing gene knock out （KO） in up to 53.3% of colonies analyzed, a quarter of which harbored biallelic modification, which was much higher than that of the traditional homologous recombination （HR）. With the aid of somatic cell nuclear transfer （SCNT） technology, three piglets with the biallelic lgM heavy chain gene mutation were produced. The piglets showed no antibody-producing B cells which indicated that the biallelic mutation of the lgM heavy chain gene effectively knocked out the function of the IgM and resulted in a B cell-deficient phenotype. Our study suggests that the CRISPR/Cas9 system combined with SCNT technology is an efficient genome-editing approach in pigs.
基金supported by a grant from the National Natural Science Foundation of China (No.81570402)a grant from the Jiangsu Key Laboratory of Xenotransplantation (BM2012116)+3 种基金grants from the Sanming Project of Medicine in Shenzhenthe Fund for High Level Medical Discipline Construction of Shenzhen (No.2016031638)the Shenzhen Foundation of Science and Technology (No.JCYJ20160229204849975 and GCZX2015043017281705)grant from the National Basic Research Program of China (2015CB559200)
文摘Unbalanced brain serotonin(5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2(TPH2). In the present study, the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer(SCNT) and 10 Tph2 targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth.However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced behavior abnomality.
文摘Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylationstate-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3Kgme2 and H3K27me2 interact with ceKDMTA in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specifieity of ceDKM7A for both H3K9me2 and H3K27me2.
