Carbenes as one of the most important class of intermediates have been widely utilized in various organic synthetic transformations.Carbene insertion-initiated ring-opening reactions of cyclic ethers offer a valuable ...Carbenes as one of the most important class of intermediates have been widely utilized in various organic synthetic transformations.Carbene insertion-initiated ring-opening reactions of cyclic ethers offer a valuable strategy for constructing new carbon-oxygen bonds.In comparison with traditional thermal or metal-mediated carbene transfer reactions,visible-light-promoted multi-component reaction strategy provides a mild and eco-friendly approach to access densely functionalized molecules.Recently,visible-light-induced multi-component carbene transfer reactions of diazo compounds have been rapidly developed and attracted a great deal of research interest of chemists owing to their advantages of simple operation,mild condition,high atom economy and rich structural diversity.This paper summarizes the recent research progress on the visible-light-promoted multi-component carbene transfer reactions of diazo compounds via ring-opening of cyclic ethers with various nucleophiles.The reaction patterns of different nucleophiles and their corresponding mechanism are described in this review.The future research direction and challenges in this area are also discussed.展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on pati...BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on patient presentation.Due to its low recurrence rate and minimal complications,MMAE has gained increasing acceptance among clinicians in recent years.This report presents a case of diplopia following MMAE due to the presence of a potential anastomotic artery,aiming to enhance awareness of this complication.CASE SUMMARY A 60-year-old male patient presented with a headache following head trauma,and cranial computed tomography revealed a left-sided CSDH.The patient underwent left MMAE;however,polyvinyl alcohol particles inadvertently flowed into the lacrimal artery through an anastomotic artery,resulting in diplopia due to impaired abduction of the left eye.The diplopia resolved by postoperative day 40.The patient’s headache resolved by postoperative day 7,and the hematoma completely resolved by postoperative day 108.CONCLUSION Potential anastomotic arteries in the middle meningeal artery(MMA)can lead to serious complications.Superselective angiography of the MMA or its branches prior to embolization is essential.Performing embolization distal to potential anastomotic sites can reduce risks,and the presence of an anastomosis may warrant coil embolization or termination of the procedure.展开更多
Purpose–The brake pipe system was an essential braking component of the railway freight trains,but the existing E-type sealing rings had problems such as insufficient low-temperature resistance,poor heat stability an...Purpose–The brake pipe system was an essential braking component of the railway freight trains,but the existing E-type sealing rings had problems such as insufficient low-temperature resistance,poor heat stability and short service life.To address these issues,low-phenyl silicone rubber was prepared and tested,and the finite element analysis and experimental studies on the sealing performance of its sealing rings were carried out.Design/methodology/approach–The low-temperature resistance and thermal stability of the prepared lowphenyl silicone rubber were studied using low-temperature tensile testing,differential scanning calorimetry,dynamic thermomechanical analysis and thermogravimetric analysis.The sealing performance of the lowphenyl silicone rubber sealing ring was studied by using finite element analysis software abaqus and experiments.Findings–The prepared low-phenyl silicone rubber sealing ring possessed excellent low-temperature resistance and thermal stability.According to the finite element analysis results,the finish of the flange sealing surface and groove outer edge should be ensured,and extrusion damage should be avoided.The sealing rings were more susceptible to damage in high compression ratio and/or low-temperature environments.When the sealing effect was ensured,a small compression ratio should be selected,and rubbers with hardness and elasticity less affected by temperature should be selected.The prepared low-phenyl silicone rubber sealing ring had zero leakage at both room temperature(RT)and�508C.Originality/value–The innovation of this study is that it provides valuable data and experience for the future development of the sealing rings used in the brake pipe flange joints of the railway freight cars in China.展开更多
Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale who...Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.展开更多
Electrochemical processes lie at the core of biological function,governing energy transduction,metabolic flux,and mo-lecular signaling.Recent advances in electrochemical science now allow these processes to be probed ...Electrochemical processes lie at the core of biological function,governing energy transduction,metabolic flux,and mo-lecular signaling.Recent advances in electrochemical science now allow these processes to be probed and controlled with unprecedented spatial,temporal,and chemical resolution.In this review,we present an integrated framework that pro-gresses from fundamental mechanisms to analytical technologies and functional modulation.We begin by outlining elec-tron transfer pathways in mitochondrial respiration,microbial extracellular electron transfer,and DNA-and protein-based charge conduction,followed by the principles of photon-electron conversion in photosynthesis and the central role of redox equilibrium in coordinating cellular responses.We then highlight electrochemical analytical strategies that enable multiscale biological characterization,including biosensing,electrochemical and scanning probe imaging,electrogenerated chemilu-minescence detection,and measurements of membrane potentials and neurotransmitter dynamics.Emerging platforms such as flexible biointerfaces,ultramicroelectrodes,and nanopore systems further extend these capabilities to in vivo and single-molecule contexts.Finally,we discuss how electrochemical inputs can be used to regulate metabolic pathways,mi-crobial and protein activities,and neural signaling,enabling precision therapeutic and bioengineering applications.Togeth-er,these developments establish electrochemistry as a powerful foundation for decoding and directing biological systems.展开更多
Young women’s physical and mental health is seriously impacted by recurrent spontaneous abortion(RSA),a prevalent obstetric complication that is becoming more commonplace worldwide.Therefore,a thorough investigation ...Young women’s physical and mental health is seriously impacted by recurrent spontaneous abortion(RSA),a prevalent obstetric complication that is becoming more commonplace worldwide.Therefore,a thorough investigation into the pathophysiology of RSA and the development of novel therapeutic strategies are imperative.Recent developments suggest that mesenchymal stem cell(MSC)-based therapies may be viable for addressing RSA.Through a variety of mechanisms,the immunological circumstances at the maternal-fetal contact can be altered,including regulating immune cell homeostasis,enhancing immune tolerance,alleviating inflammatory responses,promoting angiogenic processes,and promoting tissue regeneration.MSCs exhibit a remarkable capacity for multidifferentiation that could enhance pregnancy outcomes.This article provides compelling studies supporting the efficacy of MSC-based therapies in improving pregnancy outcomes in women with RSA.展开更多
基金Science and Technology Foundation of Guizhou Province(No.QKHJC-ZK[2024]654)Guizhou Provincial University Key Laboratory of Advanced Functional Electronic Materials(No.QJ[2023]021).
文摘Carbenes as one of the most important class of intermediates have been widely utilized in various organic synthetic transformations.Carbene insertion-initiated ring-opening reactions of cyclic ethers offer a valuable strategy for constructing new carbon-oxygen bonds.In comparison with traditional thermal or metal-mediated carbene transfer reactions,visible-light-promoted multi-component reaction strategy provides a mild and eco-friendly approach to access densely functionalized molecules.Recently,visible-light-induced multi-component carbene transfer reactions of diazo compounds have been rapidly developed and attracted a great deal of research interest of chemists owing to their advantages of simple operation,mild condition,high atom economy and rich structural diversity.This paper summarizes the recent research progress on the visible-light-promoted multi-component carbene transfer reactions of diazo compounds via ring-opening of cyclic ethers with various nucleophiles.The reaction patterns of different nucleophiles and their corresponding mechanism are described in this review.The future research direction and challenges in this area are also discussed.
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
文摘Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
文摘目的揭示道地产区宝鸡西山产柴胡Bupleurum chinense植物根际土壤细菌的群落结构和多样性,为解析西山产柴胡的道地性和生态种植提供一定理论基础。方法采用16S rDNA微生物扩增子测序初步确定根际细菌的群落组成,利用稀释分离法对根际土进行分离纯化并提取细菌DNA进行分子鉴定。结果16S rDNA微生物扩增子测序结果显示样品质量总体良好。属水平上丰度前10的分别是盖亚女神菌属Gaiella、未命名蓝细菌属unidentified_Cyanobacteria、海无柄孢囊黏细菌属Haliangium、土壤红杆菌属Solirubrobacter、假节杆菌属Pseudarthrobacter、出芽菌属Gemmata、芽生球菌属Blastococcus、类诺卡氏菌属Nocardioides、鞘氨醇单胞菌属Sphingomonas、芽单苞菌属Gemmatimonas,除土壤红杆菌属外其余均属于有益菌。代谢通路预测结果显示分布于6大类:Cellular Processes、Environmental Information Processes、Genetic information processe、Human disease、Metabolism、Organismal-system。共分离到16株根际细菌,鉴定后发现均属于芽孢杆菌属,可鉴定到种水平的有漳州芽孢杆菌、短小芽孢杆菌、沙福芽孢杆菌和嗜气芽胞杆菌4种。结论阐明了西山产柴胡根际细菌群落的组成情况,物种丰富度较高且个体分布也相对均匀。在属水平上丰度排名前10的多数为有益菌,并且成功分离得到16株芽孢杆菌属细菌,可为西山柴胡的生态种植提供理论基础。
文摘BACKGROUND Middle meningeal artery embolization(MMAE)is emerging as a promising treatment for chronic subdural hematoma(CSDH),serving both as an adjunct to surgery and as a primary therapeutic option depending on patient presentation.Due to its low recurrence rate and minimal complications,MMAE has gained increasing acceptance among clinicians in recent years.This report presents a case of diplopia following MMAE due to the presence of a potential anastomotic artery,aiming to enhance awareness of this complication.CASE SUMMARY A 60-year-old male patient presented with a headache following head trauma,and cranial computed tomography revealed a left-sided CSDH.The patient underwent left MMAE;however,polyvinyl alcohol particles inadvertently flowed into the lacrimal artery through an anastomotic artery,resulting in diplopia due to impaired abduction of the left eye.The diplopia resolved by postoperative day 40.The patient’s headache resolved by postoperative day 7,and the hematoma completely resolved by postoperative day 108.CONCLUSION Potential anastomotic arteries in the middle meningeal artery(MMA)can lead to serious complications.Superselective angiography of the MMA or its branches prior to embolization is essential.Performing embolization distal to potential anastomotic sites can reduce risks,and the presence of an anastomosis may warrant coil embolization or termination of the procedure.
基金supported by the Science and Technology Research and Development Plan of the China State Railway Group Company Limited(No.Q2023J012).
文摘Purpose–The brake pipe system was an essential braking component of the railway freight trains,but the existing E-type sealing rings had problems such as insufficient low-temperature resistance,poor heat stability and short service life.To address these issues,low-phenyl silicone rubber was prepared and tested,and the finite element analysis and experimental studies on the sealing performance of its sealing rings were carried out.Design/methodology/approach–The low-temperature resistance and thermal stability of the prepared lowphenyl silicone rubber were studied using low-temperature tensile testing,differential scanning calorimetry,dynamic thermomechanical analysis and thermogravimetric analysis.The sealing performance of the lowphenyl silicone rubber sealing ring was studied by using finite element analysis software abaqus and experiments.Findings–The prepared low-phenyl silicone rubber sealing ring possessed excellent low-temperature resistance and thermal stability.According to the finite element analysis results,the finish of the flange sealing surface and groove outer edge should be ensured,and extrusion damage should be avoided.The sealing rings were more susceptible to damage in high compression ratio and/or low-temperature environments.When the sealing effect was ensured,a small compression ratio should be selected,and rubbers with hardness and elasticity less affected by temperature should be selected.The prepared low-phenyl silicone rubber sealing ring had zero leakage at both room temperature(RT)and�508C.Originality/value–The innovation of this study is that it provides valuable data and experience for the future development of the sealing rings used in the brake pipe flange joints of the railway freight cars in China.
基金supported by the National Natural Science Foundation of China(No.82371933)the National Natural Science Foundation of Shandong Province of China(No.ZR2021MH120)+1 种基金the Taishan Scholars Project(No.tsqn202211378)the Shandong Provincial Natural Science Foundation for Excellent Young Scholars(No.ZR2024YQ075).
文摘Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.
基金supported by the National Key Research and Development Program of China(Nos.2021YFA1200101 and 2021YFA1200104)the National Natural Science Foundation of China(Nos.21635005,21890741,22174134,and 22474133)the CAS Project for Young Scientists in Basic Research(YSBR-054).
文摘Electrochemical processes lie at the core of biological function,governing energy transduction,metabolic flux,and mo-lecular signaling.Recent advances in electrochemical science now allow these processes to be probed and controlled with unprecedented spatial,temporal,and chemical resolution.In this review,we present an integrated framework that pro-gresses from fundamental mechanisms to analytical technologies and functional modulation.We begin by outlining elec-tron transfer pathways in mitochondrial respiration,microbial extracellular electron transfer,and DNA-and protein-based charge conduction,followed by the principles of photon-electron conversion in photosynthesis and the central role of redox equilibrium in coordinating cellular responses.We then highlight electrochemical analytical strategies that enable multiscale biological characterization,including biosensing,electrochemical and scanning probe imaging,electrogenerated chemilu-minescence detection,and measurements of membrane potentials and neurotransmitter dynamics.Emerging platforms such as flexible biointerfaces,ultramicroelectrodes,and nanopore systems further extend these capabilities to in vivo and single-molecule contexts.Finally,we discuss how electrochemical inputs can be used to regulate metabolic pathways,mi-crobial and protein activities,and neural signaling,enabling precision therapeutic and bioengineering applications.Togeth-er,these developments establish electrochemistry as a powerful foundation for decoding and directing biological systems.
基金Supported by the Natural Science Foundation of Liaoning Province,No.2024-MSLH-525.
文摘Young women’s physical and mental health is seriously impacted by recurrent spontaneous abortion(RSA),a prevalent obstetric complication that is becoming more commonplace worldwide.Therefore,a thorough investigation into the pathophysiology of RSA and the development of novel therapeutic strategies are imperative.Recent developments suggest that mesenchymal stem cell(MSC)-based therapies may be viable for addressing RSA.Through a variety of mechanisms,the immunological circumstances at the maternal-fetal contact can be altered,including regulating immune cell homeostasis,enhancing immune tolerance,alleviating inflammatory responses,promoting angiogenic processes,and promoting tissue regeneration.MSCs exhibit a remarkable capacity for multidifferentiation that could enhance pregnancy outcomes.This article provides compelling studies supporting the efficacy of MSC-based therapies in improving pregnancy outcomes in women with RSA.