Background:Previous studies combined integrated scRNA-seq with bulk RNAdata to screen biomarkers for cardiomyopathy.This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy(HCM...Background:Previous studies combined integrated scRNA-seq with bulk RNAdata to screen biomarkers for cardiomyopathy.This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy(HCM).Methods:Datasets GSE36961,GSE130036,GSE249925 and GSE203274 were analyzed in this study.ScRNA-seq analysis was employed to identify distinct cell populations.Differentially expression analysis was conducted to screen vascular endothelial cells(VECs)-related feature genes.After calculating VECs score,WGCNA was used to correlate gene modules with the VECs score.Key HCM biomarkers were determined using random forest analysis,and LASSO regression analyses to construct a diagnostic model based on their diagnostic efficacy and differential expression.Results:Our analysis identified nine distinct cell populations,with VECs accounting for a notably higher proportion in HCM samples.Genes associated with the VECs were enriched in the pathways related to blood vessel,immunity and cardiac function.After classifying significant gene modules based on VEC-related genes,a strong correlation between the blue module and the VECs score was detected.Notably,genes in the blue module were enriched in the pathways related tometabolism andimmune response.Key geneswith a high expression in HCM were determined by intersecting differentially expressed genes(DEGs)in HCM with those in the bluemodule.Finally,randomforest analysis and LASSO regression analysis identified five central hub genes for the diagnosis of HCM,including Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B(DYRK1B),Growth Arrest and DNA Damage Inducible Alpha(GADD45A),Influenza Virus NS1A Binding Protein(IVNS1ABP),Leiomodin 2(LMOD2),and Pleckstrin Homology Like Domain Family B Member 2(PHLDB2).Conclusion:Collectively,our study discovered novel VEC-related biomarkers for HCM and comprehensively examined the mechanisms underlying the pathogenesis of HCM.展开更多
Radiotherapy is widely used clinically, but the toxic and side effects of nonselective killing of high-energy radiation limit its application. Finding biocompatible materials to assemble radiotherapy sensitizers and s...Radiotherapy is widely used clinically, but the toxic and side effects of nonselective killing of high-energy radiation limit its application. Finding biocompatible materials to assemble radiotherapy sensitizers and studying their sensitization patterns are of great significance for the clinical application. Here, biocompatible zinc porphyrin was chosen as sub-unit to construct various dimensional coordination frameworks. By employing top-down approach, suitable nanoframeworks with various dimensional zinc porphyrin were synthesized as radiosensitizers. The experimental data showed that high-dimensional zinc porphyrin nanoframeworks exhibit higher X-ray response performance.展开更多
This paper presents some numerical simulations using Discontinuous Deformation Analysis (DDA). First, DDA was applied to reproduce a series of granular flows released in a large flume. The comparison between simulated...This paper presents some numerical simulations using Discontinuous Deformation Analysis (DDA). First, DDA was applied to reproduce a series of granular flows released in a large flume. The comparison between simulated velocity and that measured in the tests demonstrates the effectiveness of DDA on description of kinematic behavior of blocky assembly. Simulated results were highly sensitive to the shape and angularity of blocky elements. Employing unrealistic block might result in different behavior from real situation. Second, three large landslides triggered by the Wenchuan earthquake were simulated. A well agreement with field data was obtained if apparent friction coefficient determined by post-analysis was adopted.展开更多
The cyclizaion reactions of Lawesson's reagent(LR) with the substrates containing two functional groups such as hydroxy groups,amino groups, has been applied to prepare the O-P-O,N-P-N type 5-membered and 6-member...The cyclizaion reactions of Lawesson's reagent(LR) with the substrates containing two functional groups such as hydroxy groups,amino groups, has been applied to prepare the O-P-O,N-P-N type 5-membered and 6-membered phosphorus heterocycles.The heterocyclizaional possibility of LR with bifunctional compounds was also discussed.展开更多
Protein glycosylation is a critical post-translational modification that influences protein folding,localization,stability,and functional interactions by attaching glycans to specific sites.This process is crucial for...Protein glycosylation is a critical post-translational modification that influences protein folding,localization,stability,and functional interactions by attaching glycans to specific sites.This process is crucial for biological functions of glycoproteins,and aberrant glycosylation can lead to genetic disorders,immune system issues,and multi-organ pathologies.Recent advancements in glycoproteomic technologies have made the study of protein glycosylation a key focus for understanding the pathogenesis of kidney diseases.This review provides a comprehensive overview of protein glycosylation mechanisms,its biological roles,molecular pathways,and significant functions in renal physiology and pathology.It specifically highlights the dynamic changes and regulatory networks associated with aberrant glycosylation in kidney diseases such as immunoglobulin A nephropathy,diabetic kidney disease,autosomal dominant polycystic kidney disease,renal cell carcinoma,and acute kidney injury.It also evaluates the clinical applications of related technologies and biomarkers.Additionally,it discusses the challenges in developing glycosylation-targeted therapeutic strategies.Future research should focus on clarifying cell-specific glycosylation regulatory networks in the kidney,integrating glycobiology with multi-omics approaches,and improving precision diagnostics and treatment for kidney diseases.展开更多
Titanium alloys have been extensively applied due to their outstanding features,including high specific strength and corrosion resistance.However,the machining of these alloys presents challenges,leading to significan...Titanium alloys have been extensively applied due to their outstanding features,including high specific strength and corrosion resistance.However,the machining of these alloys presents challenges,leading to significant tool wear and reduced tool lifetime,ascribed to the difficult-to-machine features of Ti alloys.In the context of pursuing environmental sustainability and enhanced productivity,high-speed dry-cutting technology coupled with high-quality tool coatings are prospective.This paper comprehensively explores wear patterns and recent advancements in tool coatings for high-speed dry cutting of Ti-alloys.Key coating properties such as resistance to abrasion,adhesion,oxidation,fatigue,hot hardness,and self-adaptability are briefly introduced.Design strategies for enhancing micro-hardness,toughness,and adhesion,including nanocomposite,multilayer,and gradient architectures,are also discussed.Furthermore,the paper highlights several Boron(B)doped hard coatings as promising candidates for high-speed dry cutting against Ti-alloys,exploring the impact of B on microstructure,hardness,thermal stability,oxidation resistance,and lubrication.In summary,this work provides a systematic overview of novel B-doped tool coatings applied in highspeed dry cutting against Ti-alloys.展开更多
Radiotherapy is one of the main therapeutic methods for cancers;however,nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects.Developing low-toxicity and high-ef...Radiotherapy is one of the main therapeutic methods for cancers;however,nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects.Developing low-toxicity and high-efficiency radiosensitizers to reduce the practical dose of X-ray is a promising approach to overcoming these side effects.Here,we report the use of carboxylatecontaining organic ligands to construct one-dimensional high-Z lanthanide chains for efficient response to X-ray.The onedimensional lanthanide chains are stacked through weak interactions to form coordination nanoframeworks in the presence of polyethylenimine(PEI).The morphology and activity of the synthesized nanoframeworks can be regulated through selenium atom engineering.This study presents a promising approach for effective radiotherapy through selenium-engineering stable lanthanide nanoframeworks with precise coordination structures as radiosensitizers to mitigate X-ray side effects.展开更多
Introduction The family is the most basic unit of society and its development provides important support and impetus to social advances.China has the largest population in the world and the greatest number of families...Introduction The family is the most basic unit of society and its development provides important support and impetus to social advances.China has the largest population in the world and the greatest number of families,whose sizes,structures and types are becoming increasingly diverse and complex,keeping pace with ever-changing external circumstances.展开更多
The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox bala...The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance.Inspired by natural redox-active copper enzyme centers,we developed a Cu(Ⅰ)-Cu(Ⅱ) in situ transition system in this work.Through atom engineering,we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity.The results indicated that the synthetic Cu(Ⅰ)-Cu(Ⅱ) system could under-go in situ transition in vitro and in vivo,to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest,leading to apoptosis and overcoming cancer drug resistance.This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system.展开更多
Session-based recommendation aims to predict the next item based on a user’s limited interactions within a short period.Existing approaches use mainly recurrent neural networks(RNNs)or graph neural networks(GNNs)to m...Session-based recommendation aims to predict the next item based on a user’s limited interactions within a short period.Existing approaches use mainly recurrent neural networks(RNNs)or graph neural networks(GNNs)to model the sequential patterns or the transition relationships between items.However,such models either ignore the over-smoothing issue of GNNs,or directly use cross-entropy loss with a softmax layer for model optimization,which easily results in the over-fitting problem.To tackle the above issues,we propose a self-supervised graph learning with target-adaptive masking(SGL-TM)method.Specifically,we first construct a global graph based on all involved sessions and subsequently capture the self-supervised signals from the global connections between items,which helps supervise the model in generating accurate representations of items in the ongoing session.After that,we calculate the main supervised loss by comparing the ground truth with the predicted scores of items adjusted by our designed target-adaptive masking module.Finally,we combine the main supervised component with the auxiliary self-supervision module to obtain the final loss for optimizing the model parameters.Extensive experimental results from two benchmark datasets,Gowalla and Diginetica,indicate that SGL-TM can outperform state-of-the-art baselines in terms of Recall@20 and MRR@20,especially in short sessions.展开更多
Query suggestions help users refine their queries after they input an initial query.Previous work on query suggestion has mainly concentrated on approaches that are similarity-based or context-based,developing models ...Query suggestions help users refine their queries after they input an initial query.Previous work on query suggestion has mainly concentrated on approaches that are similarity-based or context-based,developing models that either focus on adapting to a specific user(personalization)or on diversifying query aspects in order to maximize the probability of the user being satisfied(diversification).We consider the task of generating query suggestions that are both personalized and diversified.We propose a personalized query suggestion diversification(PQSD)model,where a user's long-term search behavior is injected into a basic greedy query suggestion diversification model that considers a user's search context in their current session.Query aspects are identified through clicked documents based on the open directory project(ODP)with a latent dirichlet allocation(LDA)topic model.We quantify the improvement of our proposed PQSD model against a state-of-the-art baseline using the public america online(AOL)query log and show that it beats the baseline in terms of metrics used in query suggestion ranking and diversification.The experimental results show that PQSD achieves its best performance when only queries with clicked documents are taken as search context rather than all queries,especially when more query suggestions are returned in the list.展开更多
基金supported by Technology Project of Nantong Municipal Health Commission(grant number MSZ2022045).
文摘Background:Previous studies combined integrated scRNA-seq with bulk RNAdata to screen biomarkers for cardiomyopathy.This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy(HCM).Methods:Datasets GSE36961,GSE130036,GSE249925 and GSE203274 were analyzed in this study.ScRNA-seq analysis was employed to identify distinct cell populations.Differentially expression analysis was conducted to screen vascular endothelial cells(VECs)-related feature genes.After calculating VECs score,WGCNA was used to correlate gene modules with the VECs score.Key HCM biomarkers were determined using random forest analysis,and LASSO regression analyses to construct a diagnostic model based on their diagnostic efficacy and differential expression.Results:Our analysis identified nine distinct cell populations,with VECs accounting for a notably higher proportion in HCM samples.Genes associated with the VECs were enriched in the pathways related to blood vessel,immunity and cardiac function.After classifying significant gene modules based on VEC-related genes,a strong correlation between the blue module and the VECs score was detected.Notably,genes in the blue module were enriched in the pathways related tometabolism andimmune response.Key geneswith a high expression in HCM were determined by intersecting differentially expressed genes(DEGs)in HCM with those in the bluemodule.Finally,randomforest analysis and LASSO regression analysis identified five central hub genes for the diagnosis of HCM,including Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B(DYRK1B),Growth Arrest and DNA Damage Inducible Alpha(GADD45A),Influenza Virus NS1A Binding Protein(IVNS1ABP),Leiomodin 2(LMOD2),and Pleckstrin Homology Like Domain Family B Member 2(PHLDB2).Conclusion:Collectively,our study discovered novel VEC-related biomarkers for HCM and comprehensively examined the mechanisms underlying the pathogenesis of HCM.
基金supported by National Natural Science Foundation of China (Nos. 21877049, 22177038, 32171296)Guangdong Natural Science Foundation (Nos. 2020B1515120043, 2022A1515012235)+2 种基金Major Program for Tackling Key Problems of Industrial Technology in Guangzhou (Nos. 201902020013)Guangdong Pearl River Talent Program (No. 2017GC010354)Innovation Team Project in Guangdong Colleges and Universities (Nos. 2019KCXTD008, 2019KTSCX012)。
文摘Radiotherapy is widely used clinically, but the toxic and side effects of nonselective killing of high-energy radiation limit its application. Finding biocompatible materials to assemble radiotherapy sensitizers and studying their sensitization patterns are of great significance for the clinical application. Here, biocompatible zinc porphyrin was chosen as sub-unit to construct various dimensional coordination frameworks. By employing top-down approach, suitable nanoframeworks with various dimensional zinc porphyrin were synthesized as radiosensitizers. The experimental data showed that high-dimensional zinc porphyrin nanoframeworks exhibit higher X-ray response performance.
文摘This paper presents some numerical simulations using Discontinuous Deformation Analysis (DDA). First, DDA was applied to reproduce a series of granular flows released in a large flume. The comparison between simulated velocity and that measured in the tests demonstrates the effectiveness of DDA on description of kinematic behavior of blocky assembly. Simulated results were highly sensitive to the shape and angularity of blocky elements. Employing unrealistic block might result in different behavior from real situation. Second, three large landslides triggered by the Wenchuan earthquake were simulated. A well agreement with field data was obtained if apparent friction coefficient determined by post-analysis was adopted.
文摘The cyclizaion reactions of Lawesson's reagent(LR) with the substrates containing two functional groups such as hydroxy groups,amino groups, has been applied to prepare the O-P-O,N-P-N type 5-membered and 6-membered phosphorus heterocycles.The heterocyclizaional possibility of LR with bifunctional compounds was also discussed.
基金supported by the National Key Research and Development Program of China(grant Nos.2022YFF0608401,2022YFF0608404,2021YFF0702003-02)the National Natural Science Foundation of China(grant No.92478101).
文摘Protein glycosylation is a critical post-translational modification that influences protein folding,localization,stability,and functional interactions by attaching glycans to specific sites.This process is crucial for biological functions of glycoproteins,and aberrant glycosylation can lead to genetic disorders,immune system issues,and multi-organ pathologies.Recent advancements in glycoproteomic technologies have made the study of protein glycosylation a key focus for understanding the pathogenesis of kidney diseases.This review provides a comprehensive overview of protein glycosylation mechanisms,its biological roles,molecular pathways,and significant functions in renal physiology and pathology.It specifically highlights the dynamic changes and regulatory networks associated with aberrant glycosylation in kidney diseases such as immunoglobulin A nephropathy,diabetic kidney disease,autosomal dominant polycystic kidney disease,renal cell carcinoma,and acute kidney injury.It also evaluates the clinical applications of related technologies and biomarkers.Additionally,it discusses the challenges in developing glycosylation-targeted therapeutic strategies.Future research should focus on clarifying cell-specific glycosylation regulatory networks in the kidney,integrating glycobiology with multi-omics approaches,and improving precision diagnostics and treatment for kidney diseases.
基金supported by the Natural Science Foundation of China(No.52271047)the Natural Science Foundation of Anhui Province(No.2208085ME106).
文摘Titanium alloys have been extensively applied due to their outstanding features,including high specific strength and corrosion resistance.However,the machining of these alloys presents challenges,leading to significant tool wear and reduced tool lifetime,ascribed to the difficult-to-machine features of Ti alloys.In the context of pursuing environmental sustainability and enhanced productivity,high-speed dry-cutting technology coupled with high-quality tool coatings are prospective.This paper comprehensively explores wear patterns and recent advancements in tool coatings for high-speed dry cutting of Ti-alloys.Key coating properties such as resistance to abrasion,adhesion,oxidation,fatigue,hot hardness,and self-adaptability are briefly introduced.Design strategies for enhancing micro-hardness,toughness,and adhesion,including nanocomposite,multilayer,and gradient architectures,are also discussed.Furthermore,the paper highlights several Boron(B)doped hard coatings as promising candidates for high-speed dry cutting against Ti-alloys,exploring the impact of B on microstructure,hardness,thermal stability,oxidation resistance,and lubrication.In summary,this work provides a systematic overview of novel B-doped tool coatings applied in highspeed dry cutting against Ti-alloys.
基金supported by the National Natural Science Foundation of China(Nos.21877049,22177038,and 32171296)Guangdong Natural Science Foundation(Nos.2022A1515012235 and 2020B1515120043)+1 种基金Guangdong Pearl River Talent Program(No.2017GC010354)Innovation Team Project in Guangdong Colleges and Universities(Nos.2019KCXTD008 and 2019KTSCX012).
文摘Radiotherapy is one of the main therapeutic methods for cancers;however,nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects.Developing low-toxicity and high-efficiency radiosensitizers to reduce the practical dose of X-ray is a promising approach to overcoming these side effects.Here,we report the use of carboxylatecontaining organic ligands to construct one-dimensional high-Z lanthanide chains for efficient response to X-ray.The onedimensional lanthanide chains are stacked through weak interactions to form coordination nanoframeworks in the presence of polyethylenimine(PEI).The morphology and activity of the synthesized nanoframeworks can be regulated through selenium atom engineering.This study presents a promising approach for effective radiotherapy through selenium-engineering stable lanthanide nanoframeworks with precise coordination structures as radiosensitizers to mitigate X-ray side effects.
文摘Introduction The family is the most basic unit of society and its development provides important support and impetus to social advances.China has the largest population in the world and the greatest number of families,whose sizes,structures and types are becoming increasingly diverse and complex,keeping pace with ever-changing external circumstances.
基金supported by National Natural Science Foundation of China (21877049,22177038,32171296)Guangdong Natural Science Foundation (2020B1515120043,2022A1515012235)+2 种基金the Major Program for Tackling Key Problems of Industrial Technology in Guangzhou (201902020013)Guangdong Pearl River Talent Program(2017GC010354)the Innovation Team Project in Guangdong Colleges and Universities (2019KCXTD008,2019KTSCX012)
文摘The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance.Inspired by natural redox-active copper enzyme centers,we developed a Cu(Ⅰ)-Cu(Ⅱ) in situ transition system in this work.Through atom engineering,we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity.The results indicated that the synthetic Cu(Ⅰ)-Cu(Ⅱ) system could under-go in situ transition in vitro and in vivo,to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest,leading to apoptosis and overcoming cancer drug resistance.This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system.
文摘Session-based recommendation aims to predict the next item based on a user’s limited interactions within a short period.Existing approaches use mainly recurrent neural networks(RNNs)or graph neural networks(GNNs)to model the sequential patterns or the transition relationships between items.However,such models either ignore the over-smoothing issue of GNNs,or directly use cross-entropy loss with a softmax layer for model optimization,which easily results in the over-fitting problem.To tackle the above issues,we propose a self-supervised graph learning with target-adaptive masking(SGL-TM)method.Specifically,we first construct a global graph based on all involved sessions and subsequently capture the self-supervised signals from the global connections between items,which helps supervise the model in generating accurate representations of items in the ongoing session.After that,we calculate the main supervised loss by comparing the ground truth with the predicted scores of items adjusted by our designed target-adaptive masking module.Finally,we combine the main supervised component with the auxiliary self-supervision module to obtain the final loss for optimizing the model parameters.Extensive experimental results from two benchmark datasets,Gowalla and Diginetica,indicate that SGL-TM can outperform state-of-the-art baselines in terms of Recall@20 and MRR@20,especially in short sessions.
基金supported by the National Natural Science Foundation of China(Grant No.61702526)the National Advanced Research Project(6141B0801010b)。
文摘Query suggestions help users refine their queries after they input an initial query.Previous work on query suggestion has mainly concentrated on approaches that are similarity-based or context-based,developing models that either focus on adapting to a specific user(personalization)or on diversifying query aspects in order to maximize the probability of the user being satisfied(diversification).We consider the task of generating query suggestions that are both personalized and diversified.We propose a personalized query suggestion diversification(PQSD)model,where a user's long-term search behavior is injected into a basic greedy query suggestion diversification model that considers a user's search context in their current session.Query aspects are identified through clicked documents based on the open directory project(ODP)with a latent dirichlet allocation(LDA)topic model.We quantify the improvement of our proposed PQSD model against a state-of-the-art baseline using the public america online(AOL)query log and show that it beats the baseline in terms of metrics used in query suggestion ranking and diversification.The experimental results show that PQSD achieves its best performance when only queries with clicked documents are taken as search context rather than all queries,especially when more query suggestions are returned in the list.
