In this article,to reduce the complexity and improve the generalization ability of current gesture recognition systems,we propose a novel SE-CNN attention architecture for sEMG-based hand gesture recognition.The propo...In this article,to reduce the complexity and improve the generalization ability of current gesture recognition systems,we propose a novel SE-CNN attention architecture for sEMG-based hand gesture recognition.The proposed algorithm introduces a temporal squeeze-and-excite block into a simple CNN architecture and then utilizes it to recalibrate the weights of the feature outputs from the convolutional layer.By enhancing important features while suppressing useless ones,the model realizes gesture recognition efficiently.The last procedure of the proposed algorithm is utilizing a simple attention mechanism to enhance the learned representations of sEMG signals to performmulti-channel sEMG-based gesture recognition tasks.To evaluate the effectiveness and accuracy of the proposed algorithm,we conduct experiments involving multi-gesture datasets Ninapro DB4 and Ninapro DB5 for both inter-session validation and subject-wise cross-validation.After a series of comparisons with the previous models,the proposed algorithm effectively increases the robustness with improved gesture recognition performance and generalization ability.展开更多
Coronavirus disease 2019(COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, how...Coronavirus disease 2019(COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2(ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-Co V-2. We analyzed clinical data, genetic data, and receptor binding capability.Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal reninangiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations(V354 F and V470 A) by receptorligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354 F and V470 A mutants has increased with the development of the SARS-Co V-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.展开更多
Mechanical forces produced from cells regulate cell functions and fate for tissue development and regeneration.Knowledge in mechanobiology thus provides new strategy for diagnosis and prosthetics.In our work,we develo...Mechanical forces produced from cells regulate cell functions and fate for tissue development and regeneration.Knowledge in mechanobiology thus provides new strategy for diagnosis and prosthetics.In our work,we develop a platform which could precisely detect cellular traction force with resolution of 100 pN,enabling quantification of chemotherapy at early stage,re-epithelialization and cell collision.Additionally,a better solution for antimicrobial dressing managing infection has been provided by modifying the surface to enable both the disruption on biofilm and the elimination of engaged planktonic bacteria.Mechanobiological study demonstrated our dual-function surface remains harmless to host mammalian cells during thermalablation.Our design could pave the way further for creating soft miniaturized medical robots that defend our living system via safe interaction down to cellular level.展开更多
Dengue virus infections are increasing worldwide generally and in Asia,Central and South America and Africa,particularly.It poses a serious threat to the children population.The rapid and accurate diagnostic systems a...Dengue virus infections are increasing worldwide generally and in Asia,Central and South America and Africa,particularly.It poses a serious threat to the children population.The rapid and accurate diagnostic systems are essentially required due to lack of effective vaccine against dengue virus and the progressive spread of the dengue virus infection.The recent progress in developing micro-and nano-fabrication techniques has led to low cost and scale down the biomedical point-of-care devices.Starting from the conventional and modern available methods for the diagnosis of dengue infection,this review examines several emerging rapid and point-of-care diagnostic devices that hold significant potential for the progress in smart diagnosis tools.The given review revealed that an effective vaccine is required urgently against all the dengue virus serotypes.However,the rapid detection methods of dengue virus help in early treatment and significantly reduce the dengue virus outbreak.展开更多
Type 2 diabetes mellitus (T2DM) has become a prevalent health problem in China,especially in urban areas.Early prevention strategies are needed to reduce the associated mortality and morbidity.We applied the combinati...Type 2 diabetes mellitus (T2DM) has become a prevalent health problem in China,especially in urban areas.Early prevention strategies are needed to reduce the associated mortality and morbidity.We applied the combination of rules and different machine learning techniques to assess the risk of development of T2DM in an urban Chinese adult population.A retrospective analysis was performed on 8000 people with non-diabetes and 3845 people with T2DM in Nanjing.Multilayer Perceptron (MLP),AdaBoost (AD),Trees Random Forest (TRF),Support Vector Machine (SVM),and Gradient Tree Boosting (GTB) machine learning techniques with 10 cross validation methods were used with the proposed model for the prediction of the risk of development of T2DM.The performance of these models was evaluated with accuracy,precision,sensitivity,specificity,and area under receiver operating characteristic (ROC) curve (AUC).After comparison,the prediction accuracy of the different five machine models was 0.87,0.86,0.86,0.86 and 0.86 respectively.The combination model using the same voting weight of each component was built on T2DM,which was performed better than individual models.The findings indicate that,combining machine learning models could provide an accurate assessment model for T2DM risk prediction.展开更多
Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical...Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.展开更多
Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the car...Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.展开更多
Circular RNAs(circ RNAs),covalently closed continuous RNA loops,are generated from cognate linear RNAs through back splicing events,and alternative splicing events may generate different circ RNA isoforms at the same ...Circular RNAs(circ RNAs),covalently closed continuous RNA loops,are generated from cognate linear RNAs through back splicing events,and alternative splicing events may generate different circ RNA isoforms at the same locus.However,the challenges of reconstruction and quantification of alternatively spliced full-length circ RNAs remain unresolved.On the basis of the internal structural characteristics of circ RNAs,we developed Circ AST,a tool to assemble alternatively spliced circ RNA transcripts and estimate their expression by using multiple splice graphs.Simulation studies showed that Circ AST correctly assembled the full sequences of circ RNAs with a sensitivity of 85.63%–94.32%and a precision of 81.96%–87.55%.By assigning reads to specific isoforms,Circ AST quantified the expression of circ RNA isoforms with correlation coefficients of 0.85–0.99 between theoretical and estimated values.We evaluated Circ AST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circ RNAs and identified 380 circ RNAs with full-length sequences different from those of their corresponding cognate linear RNAs.RT-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms,thus further indicating the good performance of Circ AST,especially for isoforms with low abundance.We also applied Circ AST to published experimental data and observed substantial diversity in circular transcripts across samples,thus suggesting that circ RNA expression is highly regulated.Circ AST can be accessed freely at https://github--com.3pco.8686c.com/xiaofengsong/CircAST.展开更多
With unique physicochemical properties and biological effects,magnetic nanomaterials(MNMs)play a crucial role in the biomedical field.In particular,magnetic iron oxide nanoparticles(MIONPs)are approved by the United S...With unique physicochemical properties and biological effects,magnetic nanomaterials(MNMs)play a crucial role in the biomedical field.In particular,magnetic iron oxide nanoparticles(MIONPs)are approved by the United States Food and Drug Administration(FDA)for clinical applications at present due to their low toxicity,biocompatibility,and biodegradability.Despite the unarguable effectiveness,massive space for improving such materials'performance still needs to be filled.Recently,many efforts have been devoted to improving the preparation methods based on the materials'biosafety.Besides,researchers have successfully.regulated the performance of magnetic nanoparticles(MNPs)by changing their sizes,morphologies,compositions;or by.aggregating as-synthesized MNPs in an orderly arrangement to meet various clinical requirements.The rise of cloud computing and artificial intelligence techniques provides novel ways for fast material characterization,automated data analysis,and mechanism demonstration.In this review,we summarized the studies that focused on the preparation routes and performance regulations of high-quality MNPs,and their special properties applied in biomedical detection,diagnosis,and treatment.At the same time,the future.development of MNMs was also discussed.展开更多
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integr...Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.展开更多
Controlling the phase of light in magnetoplasmonic structures is receiving increasing attention because of its already shown capability in ultrasensitive and label-free molecular-level detection.Magneto-optical Kerr r...Controlling the phase of light in magnetoplasmonic structures is receiving increasing attention because of its already shown capability in ultrasensitive and label-free molecular-level detection.Magneto-optical Kerr reversal has been achieved and well explained in nanodisks by using the phase of localized plasmons.In this paper,we report that the Kerr reversal can also be produced by surface plasmon polaritons independently.We experimentally confirm this in Co and Ag/Co/Ag metal nanogratings,and can give a qualitative explanation that it is the charge accumulation at the interface between the grating surface and air that acts as the electromagnetic restoring force to contribute necessary additional phase for Kerr reversal.Our finding can enrich the means of designing and fabricating magneto-optical-based biochemical sensors.展开更多
Macrophage polarization is an essential process involved in immune regulation.In response to different microenvironmental stimulation,macrophages polarize into cells with different phenotypes and functions,most typica...Macrophage polarization is an essential process involved in immune regulation.In response to different microenvironmental stimulation,macrophages polarize into cells with different phenotypes and functions,most typically M1(pro-inflammatory)and M2(anti-inflammatory)macrophages.Iron-based nanoparticles have been widely explored and reported to regulatemacrophage polarization for various biomedical applications.However,the influence factors and modulation mechanisms behind are complicated and not clear.In this review,we systemically summarized different iron-based nanoparticles that regulate macrophage polarization and function and discussed the influence factors and mechanisms underlying the modulation process.This review aims to deepen the understanding of the modulation of macrophage polarization by iron-based nanoparticles and expects to provide evidence and guidance for subsequent design and application of iron-based nanoparticles with specific macrophage modulation functions.展开更多
Objective:To explore treatment planning approaches using volumetric modulated arc therapy(VMAT)for head and neck cancer patients with metallic dental fillings.Methods:Fifty-six patients with metallic dental fillings t...Objective:To explore treatment planning approaches using volumetric modulated arc therapy(VMAT)for head and neck cancer patients with metallic dental fillings.Methods:Fifty-six patients with metallic dental fillings treated with radiotherapy were selected,and three VMAT plans,the jaw-tracking plan,fixed-jaw plan,and non-coplanar plan,were designed for each patient.In the jawtracking plan,two coplanar partial arc fields that avoid the metal area were set,and the jaw was automatically tracked.In the fixed-jaw plan,different fields were set in three sections according to the fixed-jaw method.The fields were the same as those in the jaw-tracking plan for the section containing metal implants,while full arc fields were set in the nonmetal sections.In the non-coplanar plan,a non-coplanar arc field was added based on the jaw-tracking plan.The treatment plan in the jaw-tracking plan was optimized,and the constraints on the planning target volume(PTV)or organs at risk(OARs)in the jaw-tracking plan were copied to the other two plans.The dose distribution in PTV and OARs of the patients in the three treatment plans was compared.Results:There were no significant differences in the maximum doses to the spinal cord or optic nerves among the three treatment plans.However,compared with the jaw-tracking plan,the fixed-jaw plan showed lower mean doses to the pharynx[(42.9±7.1)Gy vs.(44.1±7.1)Gy,P<0.05]and larynx[(43.9±3.9)Gy vs.(45.4±4.7)Gy,P<0.05],while the non-coplanar plan obtained significantly better dose distribution in PTV and all OARs except for the spinal cord and optic nerves.Meanwhile,the non-coplanar plan performed significantly better than the fixed-jaw plan in terms of the maximum doses to the brainstem[(50.24.0)Gy vs.(51.4±4.6)Gy,P<0.05],left lens[(5.8±0.2)Gy vs.(6.3±0.4 Gy),P<0.05],and right lens[(5.9±0.3)Gy vs.(6.2±0.3)Gy,P<0.05].Conclusions:The non-coplanar VMAT is an optimal method for treating head and neck cancer patients with metallic dental fillings since it can provide better dose distribution in PTV and reduce doses to OARs.展开更多
Lignin exhibits antioxidative and various other biological properties.However,its neuroprotection capability has rarely been studied.In this study,three types of lignin with different structures were prepared from gra...Lignin exhibits antioxidative and various other biological properties.However,its neuroprotection capability has rarely been studied.In this study,three types of lignin with different structures were prepared from grape seeds by using different isolation techniques.The antioxidative and neuroprotective effects of the lignin fractions were evaluated with the apoptosis model of murine neuroectodermal(NE-4C)neural stem cells stimulated with bisphenol AF.The results demonstrated that the half maximal inhibitory concentration for scavenging 2,2-diphenyl-1-picrylhydrazyl with water-soluble lignin(L-W,58.19μg·mL^(–1))was lower than those of lignin in the autohydrolyzed residue of grape seeds(84.27μg·mL^(–1))and original lignin in grape seeds(99.44μg·mL^(–1)).BPAF exposure had negative effects on the reactive oxygen species,malondialdehyde content,and superoxide dismutase and glutathione peroxidase activities in NE-4C cells,which can be reversed by using the prepared lignin to reduce oxidative stress.An immunofluorescence assay demonstrated that grape seed lignin induced protective effects on BPAF-injured NE-4C cells via the nuclear factor erythroid 2-related Factor 2 pathway.In addition,correlational analyses showed that lignin(L-W)with lower molecular weights and noncondensed phenolic hydroxyl group content and higher contents of COOH groups effectively prevented cell apoptosis,scavenged reactive oxygen species,and ensured protection from nerve injury.This study demonstrated that grape seed lignin can be used as a neuroprotective agent and serves as a demonstration of active lignin production from grape seed waste.展开更多
Labeling of mesenchymal stem cells(MSCs)with superparamagnetic iron oxide nanoparticles(SPIONs)has emerged as a potential method for magnetic resonance imaging(MRI)tracking of transplanted cells in tissue repair studi...Labeling of mesenchymal stem cells(MSCs)with superparamagnetic iron oxide nanoparticles(SPIONs)has emerged as a potential method for magnetic resonance imaging(MRI)tracking of transplanted cells in tissue repair studies and clinical trials.Labeling of MSCs using clinically approved SPIONs(ferumoxytol)requires the use of transfection reagents or magnetic field,which largely limits their clinical application.To overcome this obstacle,we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol.Unlike conventional methods,ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids.Moreover,the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety.Strikingly,the encapsulated ferumoxytol was localized in the extracellular matrix(ECM)of the spheroids instead of the cytoplasm,minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids.This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.展开更多
Covalent adaptable networks(CANs),which combine the benefits of traditional thermosets and thermoplastics,have attracted considerable attention.The dynamics of reversible covalent bonds and mobility of polymer chains ...Covalent adaptable networks(CANs),which combine the benefits of traditional thermosets and thermoplastics,have attracted considerable attention.The dynamics of reversible covalent bonds and mobility of polymer chains in CANs determine the topological rearrangement of the polymeric network,which is critical to their superior features,such as self-healing and reprocessing.Herein,we introduce an ionic liquid to dimethylglyoximeurethane(DOU)-based CANs to regulate both reversible bond dynamics and polymer chain mobility by cooperative chemical coupling and physical lubrication.Small-molecule model experiments demonstrated that ionic liquids can catalyze dynamic DOU bond exchange.Ionic liquid also breaks the hydrogen bonds between polymeric chains,thereby increasing their mobility.As a combined result,the activation energy of the dissociation of the dynamic network decreased from 110 to 85 kJ mol^(−1).Furthermore,as a functional moiety,the ionic liquid imparts new properties to CANs and will greatly expand their applications.For example,the consequent conductivity of resultant ionic CAN(iCAN)has demonstrated a great power to build high-performance multifunctional wearable electronics responsive to multiple stimulations including temperature,strain,and humidity.This study provides a new design principle that simultaneously uses the chemical and physical effects of two structural components to regulate material properties enabling novel applications.展开更多
Primary biliary cholangitis(PBC)is an autoimmune liver disease characterized by the destruction of intrahepatic small bile ducts and progressive cholestasis,eventually leading to liver cirrhosis and hepatic failure wi...Primary biliary cholangitis(PBC)is an autoimmune liver disease characterized by the destruction of intrahepatic small bile ducts and progressive cholestasis,eventually leading to liver cirrhosis and hepatic failure without appropriate treatment(Terziroli Beretta-Piccoli et al.,2019).展开更多
Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unst...Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.展开更多
Let E be the Engel group and D be a bracket generating left invariant distribution with a Lorentzian metric, which is a nondegenerate metric of index 1. In this paper, the author constructs a parametrization of a quas...Let E be the Engel group and D be a bracket generating left invariant distribution with a Lorentzian metric, which is a nondegenerate metric of index 1. In this paper, the author constructs a parametrization of a quasi-pendulum equation by Jacobi functions, and then gets the space-like Hamiltonian geodesics in the Engel group with a sub-Lorentzian metric.展开更多
基金funded by the National Key Research and Development Program of China(2017YFB1303200)NSFC(81871444,62071241,62075098,and 62001240)+1 种基金Leading-Edge Technology and Basic Research Program of Jiangsu(BK20192004D)Jiangsu Graduate Scientific Research Innovation Programme(KYCX20_1391,KYCX21_1557).
文摘In this article,to reduce the complexity and improve the generalization ability of current gesture recognition systems,we propose a novel SE-CNN attention architecture for sEMG-based hand gesture recognition.The proposed algorithm introduces a temporal squeeze-and-excite block into a simple CNN architecture and then utilizes it to recalibrate the weights of the feature outputs from the convolutional layer.By enhancing important features while suppressing useless ones,the model realizes gesture recognition efficiently.The last procedure of the proposed algorithm is utilizing a simple attention mechanism to enhance the learned representations of sEMG signals to performmulti-channel sEMG-based gesture recognition tasks.To evaluate the effectiveness and accuracy of the proposed algorithm,we conduct experiments involving multi-gesture datasets Ninapro DB4 and Ninapro DB5 for both inter-session validation and subject-wise cross-validation.After a series of comparisons with the previous models,the proposed algorithm effectively increases the robustness with improved gesture recognition performance and generalization ability.
基金supported by the National Key Research and Development Program of China (2018YFD0900602)National Natural Science Foundation of China (31970388, 31701234)+3 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)Natural Science Foundation of the Jiangsu Higher Education Institutions (17KJB180006)Natural Science Foundation from Jiangsu Province (BK20160043, BK20151546, 15KJA180004and BK20171035)Jiangsu Distinguished Professor Funding。
文摘Coronavirus disease 2019(COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2(ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-Co V-2. We analyzed clinical data, genetic data, and receptor binding capability.Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal reninangiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations(V354 F and V470 A) by receptorligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354 F and V470 A mutants has increased with the development of the SARS-Co V-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.
基金financially supported by the NTU-Northwestern Institute for Nanomedicine ( NRF-NRFI2017-07)Startup Foundation of Nanjing Medical University
文摘Mechanical forces produced from cells regulate cell functions and fate for tissue development and regeneration.Knowledge in mechanobiology thus provides new strategy for diagnosis and prosthetics.In our work,we develop a platform which could precisely detect cellular traction force with resolution of 100 pN,enabling quantification of chemotherapy at early stage,re-epithelialization and cell collision.Additionally,a better solution for antimicrobial dressing managing infection has been provided by modifying the surface to enable both the disruption on biofilm and the elimination of engaged planktonic bacteria.Mechanobiological study demonstrated our dual-function surface remains harmless to host mammalian cells during thermalablation.Our design could pave the way further for creating soft miniaturized medical robots that defend our living system via safe interaction down to cellular level.
基金supported by the Scientific Research Fund of the Shenzhen International cooperation projects under Grant Nos.(GJHZ20190819151403615)the Natural Science Youth Foundation of China(61801307).
文摘Dengue virus infections are increasing worldwide generally and in Asia,Central and South America and Africa,particularly.It poses a serious threat to the children population.The rapid and accurate diagnostic systems are essentially required due to lack of effective vaccine against dengue virus and the progressive spread of the dengue virus infection.The recent progress in developing micro-and nano-fabrication techniques has led to low cost and scale down the biomedical point-of-care devices.Starting from the conventional and modern available methods for the diagnosis of dengue infection,this review examines several emerging rapid and point-of-care diagnostic devices that hold significant potential for the progress in smart diagnosis tools.The given review revealed that an effective vaccine is required urgently against all the dengue virus serotypes.However,the rapid detection methods of dengue virus help in early treatment and significantly reduce the dengue virus outbreak.
基金This work was supported by grants from the National Natural Science Foundation of China (No.81570737, No.81370947, No.81570736, No.81770819, No.81500612, No.81400832, No.81600637, No.81600632, and No.81703294)the National Key Research and Development Program of China (No.2016YFC1304804 and No.2017YFC1309605)+4 种基金the Jiangsu Provincial Key Medical Discipline (No.ZDXKB2016012)the Key Project of Nanjing Clinical Medical Sciencethe Key Research and Development Program of Jiangsu Province of China (No.BE2015604 and No.BE2016606)the Jiangsu Provincial Medical Talent (No.ZDRCA2016062)the Nanjing Science and Technology Development Project (No.201605019).
文摘Type 2 diabetes mellitus (T2DM) has become a prevalent health problem in China,especially in urban areas.Early prevention strategies are needed to reduce the associated mortality and morbidity.We applied the combination of rules and different machine learning techniques to assess the risk of development of T2DM in an urban Chinese adult population.A retrospective analysis was performed on 8000 people with non-diabetes and 3845 people with T2DM in Nanjing.Multilayer Perceptron (MLP),AdaBoost (AD),Trees Random Forest (TRF),Support Vector Machine (SVM),and Gradient Tree Boosting (GTB) machine learning techniques with 10 cross validation methods were used with the proposed model for the prediction of the risk of development of T2DM.The performance of these models was evaluated with accuracy,precision,sensitivity,specificity,and area under receiver operating characteristic (ROC) curve (AUC).After comparison,the prediction accuracy of the different five machine models was 0.87,0.86,0.86,0.86 and 0.86 respectively.The combination model using the same voting weight of each component was built on T2DM,which was performed better than individual models.The findings indicate that,combining machine learning models could provide an accurate assessment model for T2DM risk prediction.
基金This research was funded by the Key Research and Development Plan of Jiangsu Province under grant BE2017735.Q.S.conceived the study and wrote the manuscript.Q.S.,C.C.,H.G.X.W.collected,analyzed,and interpreted the data.H.G.and X.W.contributed substantially to the development of ECG signal conversion Matlab software and remote automatic detection algorithm.J.L.,M.C.and C.L.revised the manuscript,evaluated and supervised the study.
文摘Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.
基金supported by the National Natural Science Foundation of China(Grant Nos.81902836 and 81572602)the China Postdoctoral Science Foundation(Grant Nos.2017M610339 and 2018M630584)。
文摘Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.
基金the National Natural Science Foundation of China(Grant No.61571223)the National Key R&D Program of China(Grant No.2016YFA0503300)+4 种基金supported by the National Natural Science Foundation of China(Grant Nos.61171191,31471403,and 81771641)the 333 Project of Jiangsu Province(Grant No.BRA2016386)the Program for Distinguished Talents of Six Domains in Jiangsu Province(Grant No.YY-019)the Fundamental Research Funds for the Central Universities(Grant No.NP2018109)the Fok Ying Tung Education Foundation(Grant No.161037),China.
文摘Circular RNAs(circ RNAs),covalently closed continuous RNA loops,are generated from cognate linear RNAs through back splicing events,and alternative splicing events may generate different circ RNA isoforms at the same locus.However,the challenges of reconstruction and quantification of alternatively spliced full-length circ RNAs remain unresolved.On the basis of the internal structural characteristics of circ RNAs,we developed Circ AST,a tool to assemble alternatively spliced circ RNA transcripts and estimate their expression by using multiple splice graphs.Simulation studies showed that Circ AST correctly assembled the full sequences of circ RNAs with a sensitivity of 85.63%–94.32%and a precision of 81.96%–87.55%.By assigning reads to specific isoforms,Circ AST quantified the expression of circ RNA isoforms with correlation coefficients of 0.85–0.99 between theoretical and estimated values.We evaluated Circ AST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circ RNAs and identified 380 circ RNAs with full-length sequences different from those of their corresponding cognate linear RNAs.RT-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms,thus further indicating the good performance of Circ AST,especially for isoforms with low abundance.We also applied Circ AST to published experimental data and observed substantial diversity in circular transcripts across samples,thus suggesting that circ RNA expression is highly regulated.Circ AST can be accessed freely at https://github--com.3pco.8686c.com/xiaofengsong/CircAST.
基金supported by the National Key Research and Development Program of China(No.2017YFA0104302)the National Natural Science Foundation of China(Nos.51832001,61821002,and 31800843)。
文摘With unique physicochemical properties and biological effects,magnetic nanomaterials(MNMs)play a crucial role in the biomedical field.In particular,magnetic iron oxide nanoparticles(MIONPs)are approved by the United States Food and Drug Administration(FDA)for clinical applications at present due to their low toxicity,biocompatibility,and biodegradability.Despite the unarguable effectiveness,massive space for improving such materials'performance still needs to be filled.Recently,many efforts have been devoted to improving the preparation methods based on the materials'biosafety.Besides,researchers have successfully.regulated the performance of magnetic nanoparticles(MNPs)by changing their sizes,morphologies,compositions;or by.aggregating as-synthesized MNPs in an orderly arrangement to meet various clinical requirements.The rise of cloud computing and artificial intelligence techniques provides novel ways for fast material characterization,automated data analysis,and mechanism demonstration.In this review,we summarized the studies that focused on the preparation routes and performance regulations of high-quality MNPs,and their special properties applied in biomedical detection,diagnosis,and treatment.At the same time,the future.development of MNMs was also discussed.
基金the Key International(Regional)Cooperative Research Project(No.81820108028)the National Natural Science Foundation of China(Nos.81521004,81922061,81973123,and 81803306)+2 种基金the Science Foundation for Distinguished Young Scholars of Jiangsu(No.BK20160046)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).the National Cancer Institute,National Institutes of Health of USA through grants U01-CA063673,UM1-CA167462,and U01-CA167462.
文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
基金Project supported by the National Natural Science Foundation of China(Grant No.11374146)the China Postdoctoral Science Foundation(Grant No.2018M632278)the Jiangsu Provincial Planned Projects for Postdoctoral Research Funds,China(Grant No.1701092C)
文摘Controlling the phase of light in magnetoplasmonic structures is receiving increasing attention because of its already shown capability in ultrasensitive and label-free molecular-level detection.Magneto-optical Kerr reversal has been achieved and well explained in nanodisks by using the phase of localized plasmons.In this paper,we report that the Kerr reversal can also be produced by surface plasmon polaritons independently.We experimentally confirm this in Co and Ag/Co/Ag metal nanogratings,and can give a qualitative explanation that it is the charge accumulation at the interface between the grating surface and air that acts as the electromagnetic restoring force to contribute necessary additional phase for Kerr reversal.Our finding can enrich the means of designing and fabricating magneto-optical-based biochemical sensors.
基金supported by the National Natural Science Foundation of China(51832001,61821002)the Natural Science Foundation of Jiangsu Province(BK20220824,BK20222002)+1 种基金the National Key Research and Development Project(2021YFA1201403,2021YFA0716304)the Nanjing Science and technology development Foundation(202205066).
文摘Macrophage polarization is an essential process involved in immune regulation.In response to different microenvironmental stimulation,macrophages polarize into cells with different phenotypes and functions,most typically M1(pro-inflammatory)and M2(anti-inflammatory)macrophages.Iron-based nanoparticles have been widely explored and reported to regulatemacrophage polarization for various biomedical applications.However,the influence factors and modulation mechanisms behind are complicated and not clear.In this review,we systemically summarized different iron-based nanoparticles that regulate macrophage polarization and function and discussed the influence factors and mechanisms underlying the modulation process.This review aims to deepen the understanding of the modulation of macrophage polarization by iron-based nanoparticles and expects to provide evidence and guidance for subsequent design and application of iron-based nanoparticles with specific macrophage modulation functions.
基金This work was funded by the General Program of Jiangsu Provincial Health Commission(No.M2020006)Changzhou Key Laboratory of Medical Physics(No.CM20193005)+2 种基金Changzhou Sci&Tech Program(No.CJ20200099)Young Talent Development Plan of Changzhou Health Commission(Nos.CZQM2020075 and CZQM2020067)the Science and Technology Programs for Young Talents of Changzhou Health Commission(No.QN201932).
文摘Objective:To explore treatment planning approaches using volumetric modulated arc therapy(VMAT)for head and neck cancer patients with metallic dental fillings.Methods:Fifty-six patients with metallic dental fillings treated with radiotherapy were selected,and three VMAT plans,the jaw-tracking plan,fixed-jaw plan,and non-coplanar plan,were designed for each patient.In the jawtracking plan,two coplanar partial arc fields that avoid the metal area were set,and the jaw was automatically tracked.In the fixed-jaw plan,different fields were set in three sections according to the fixed-jaw method.The fields were the same as those in the jaw-tracking plan for the section containing metal implants,while full arc fields were set in the nonmetal sections.In the non-coplanar plan,a non-coplanar arc field was added based on the jaw-tracking plan.The treatment plan in the jaw-tracking plan was optimized,and the constraints on the planning target volume(PTV)or organs at risk(OARs)in the jaw-tracking plan were copied to the other two plans.The dose distribution in PTV and OARs of the patients in the three treatment plans was compared.Results:There were no significant differences in the maximum doses to the spinal cord or optic nerves among the three treatment plans.However,compared with the jaw-tracking plan,the fixed-jaw plan showed lower mean doses to the pharynx[(42.9±7.1)Gy vs.(44.1±7.1)Gy,P<0.05]and larynx[(43.9±3.9)Gy vs.(45.4±4.7)Gy,P<0.05],while the non-coplanar plan obtained significantly better dose distribution in PTV and all OARs except for the spinal cord and optic nerves.Meanwhile,the non-coplanar plan performed significantly better than the fixed-jaw plan in terms of the maximum doses to the brainstem[(50.24.0)Gy vs.(51.4±4.6)Gy,P<0.05],left lens[(5.8±0.2)Gy vs.(6.3±0.4 Gy),P<0.05],and right lens[(5.9±0.3)Gy vs.(6.2±0.3)Gy,P<0.05].Conclusions:The non-coplanar VMAT is an optimal method for treating head and neck cancer patients with metallic dental fillings since it can provide better dose distribution in PTV and reduce doses to OARs.
基金This work was sponsored by the National Natural Science Foundation of China for Youth(Grant No.81901873)the Jiangsu Qing Lan Project(for Dr.Caoxing Huang)the Young Elite Scientists Sponsorship Program by CAST(for Dr.Caoxing Huang).
文摘Lignin exhibits antioxidative and various other biological properties.However,its neuroprotection capability has rarely been studied.In this study,three types of lignin with different structures were prepared from grape seeds by using different isolation techniques.The antioxidative and neuroprotective effects of the lignin fractions were evaluated with the apoptosis model of murine neuroectodermal(NE-4C)neural stem cells stimulated with bisphenol AF.The results demonstrated that the half maximal inhibitory concentration for scavenging 2,2-diphenyl-1-picrylhydrazyl with water-soluble lignin(L-W,58.19μg·mL^(–1))was lower than those of lignin in the autohydrolyzed residue of grape seeds(84.27μg·mL^(–1))and original lignin in grape seeds(99.44μg·mL^(–1)).BPAF exposure had negative effects on the reactive oxygen species,malondialdehyde content,and superoxide dismutase and glutathione peroxidase activities in NE-4C cells,which can be reversed by using the prepared lignin to reduce oxidative stress.An immunofluorescence assay demonstrated that grape seed lignin induced protective effects on BPAF-injured NE-4C cells via the nuclear factor erythroid 2-related Factor 2 pathway.In addition,correlational analyses showed that lignin(L-W)with lower molecular weights and noncondensed phenolic hydroxyl group content and higher contents of COOH groups effectively prevented cell apoptosis,scavenged reactive oxygen species,and ensured protection from nerve injury.This study demonstrated that grape seed lignin can be used as a neuroprotective agent and serves as a demonstration of active lignin production from grape seed waste.
基金supported by the National Key Research and Development Program of China(2017YFA0104302)the National Natural Science Foundation of China(51832001,61821002,81870807),the China Postdoctoral Science Foundation(2017M621787)the Talent Introduction Foundation of Nanjing Medical University(2017RC07).
文摘Labeling of mesenchymal stem cells(MSCs)with superparamagnetic iron oxide nanoparticles(SPIONs)has emerged as a potential method for magnetic resonance imaging(MRI)tracking of transplanted cells in tissue repair studies and clinical trials.Labeling of MSCs using clinically approved SPIONs(ferumoxytol)requires the use of transfection reagents or magnetic field,which largely limits their clinical application.To overcome this obstacle,we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol.Unlike conventional methods,ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids.Moreover,the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety.Strikingly,the encapsulated ferumoxytol was localized in the extracellular matrix(ECM)of the spheroids instead of the cytoplasm,minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids.This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.
基金supported by the National Key Research and Development Program of China(grant no.2021YFC2101800)the National Natural Science Foundation of China(grant nos.52173117,51733002,52073049,81971701)+7 种基金the Natural Science Foundation of Shanghai(grant nos.20ZR1402500,22ZR1400700)Shanghai Rising-Star Program(grant no.21QA1400200)Belt&Road Young Scientist Exchanges Project of Science and Technology Commission Foundation of Shanghai(grant no.20520741000)Ningbo 2025 Science and Technology Major Project(grant no.2019B10068)Science and Technology Commission of Shanghai Municipality(grant nos.20DZ2254900,20DZ2270800)the Fundamental Research Funds for the Central Universities(grant no.2232021G-02)DHU Distinguished Young Professor Program(grant no.LZA2019001)the Natural Science Funding of Jiangsu Province Grant(grant no.BK20201352).
文摘Covalent adaptable networks(CANs),which combine the benefits of traditional thermosets and thermoplastics,have attracted considerable attention.The dynamics of reversible covalent bonds and mobility of polymer chains in CANs determine the topological rearrangement of the polymeric network,which is critical to their superior features,such as self-healing and reprocessing.Herein,we introduce an ionic liquid to dimethylglyoximeurethane(DOU)-based CANs to regulate both reversible bond dynamics and polymer chain mobility by cooperative chemical coupling and physical lubrication.Small-molecule model experiments demonstrated that ionic liquids can catalyze dynamic DOU bond exchange.Ionic liquid also breaks the hydrogen bonds between polymeric chains,thereby increasing their mobility.As a combined result,the activation energy of the dissociation of the dynamic network decreased from 110 to 85 kJ mol^(−1).Furthermore,as a functional moiety,the ionic liquid imparts new properties to CANs and will greatly expand their applications.For example,the consequent conductivity of resultant ionic CAN(iCAN)has demonstrated a great power to build high-performance multifunctional wearable electronics responsive to multiple stimulations including temperature,strain,and humidity.This study provides a new design principle that simultaneously uses the chemical and physical effects of two structural components to regulate material properties enabling novel applications.
基金supported by grants from the National Natural Science Foundation of China,China(Nos.81870397,82000534,and 82073156)Shenzhen Kangzhe Pharmaceutical Co.Ltd,China(URC-126/PBC)+1 种基金The Fifth Suzhou Health Talent Project(GSWS201903)The Suzhou Radiotherapy Clinical Medical Center Project,Suzhou,Jiangsu,China(Szlcyxzx202103).
文摘Primary biliary cholangitis(PBC)is an autoimmune liver disease characterized by the destruction of intrahepatic small bile ducts and progressive cholestasis,eventually leading to liver cirrhosis and hepatic failure without appropriate treatment(Terziroli Beretta-Piccoli et al.,2019).
基金financial supports from the National Key Research and Development Program of China(2019YFA0210103 and 2017YFA0104302)the National Natural Science Foundation of China(81901873,51832001,and 81971701)+2 种基金the National Key Laboratory of Science and Technology on Strong Electromagnetic Environment Simulation and Protection(6142205190402)the Natural Science Foundation of Jiangsu Province(BK20201352)the Program of Jiangsu Specially Appointed Professor。
基金This work was financially supported by the National Natural Science Innovative Research Group Project(No.61821002)the Key Project of the National Natural Science Foundation of China(No.92163213)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20220824)the Nanjing Science and Technology Develop-ment Foundation(No.202205066).
文摘Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.
基金supported by the Science and Technology Development Fund of Nanjing Medical University(No.2017NJMU005).
文摘Let E be the Engel group and D be a bracket generating left invariant distribution with a Lorentzian metric, which is a nondegenerate metric of index 1. In this paper, the author constructs a parametrization of a quasi-pendulum equation by Jacobi functions, and then gets the space-like Hamiltonian geodesics in the Engel group with a sub-Lorentzian metric.