Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation.The purpose of this study was to explore whether aggregation...Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation.The purpose of this study was to explore whether aggregation-induced emission luminogens(AIEgens)can be used for highly specific imaging of MSU crystals to assist in the diagnosis of gout.First,we developed a series of luminogens(i.e.,tetraphenyl ethylene(TPE)-NH_(2),TPE-2NH_(2),TPE-4NH_(2),TPE-COOH,TPE-2COOH,TPE-4COOH,and TPE-Ketoalkyne),each of which was then evenly mixed with MSU crystals.Next,optimal fluorescence imaging of each of the luminogens was characterized by a confocal laser scanning microscope(CLSM).This approach was used for imaging standard samples of MSU,hydroxyapatite(HAP)crystals,and mixed samples with 1:1 mass ratio of MSU/HAP.We also imaged samples from mouse models of acute gouty arthritis,HAP deposition disease,and comorbidities of interest.Subsequently,CLSM imaging results were compared with those of compensated polarized light microscopy,and we assessed the biosafety of TPE-Ketoalkyne in the RAW264.7 cell line.Finally,CLSM time series and three-dimensional imaging were performed on MSU crystal samples from human gouty synovial fluid and tophi.As a promising candidate for MSU crystal labeling,TPE-Ketoalkyne was found to detect MSU crystals accurately and rapidly in standard samples,animal samples,and human samples,and could precisely distinguish gout from HAP deposition disease.This work demonstrates that TPE-Ketoalkyne is suitable for highly specific and timely imaging of MSU crystals in gouty arthritis and may facilitate future research on MSU crystal-related diseases.展开更多
BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture...BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.展开更多
Electroencephalogram signals are time-varying complex electrophysiological signals. Existing studies show that approximate entropy, which is a nonlinear dynamics index, is not an ideal method for electroencephalogram ...Electroencephalogram signals are time-varying complex electrophysiological signals. Existing studies show that approximate entropy, which is a nonlinear dynamics index, is not an ideal method for electroencephalogram analysis. Clinical electroencephalogram measurements usually contain electrical interference signals, creating additional challenges in terms of maintaining robustness of the analytic methods. There is an urgent need for a novel method of nonlinear dynamical analysis of the electroencephalogram that can characterize seizure-related changes in cerebral dynamics. The aim of this paper was to study the fluctuations of approximate entropy in preictal, ictal, and postictal electroencephalogram signals from a patient with absence seizures, and to improve the algorithm used to calculate the approximate entropy. The approximate entropy algorithm, especially our modified version, could accurately describe the dynamical changes of the brain during absence seizures. We could also demonstrate that the complexity of the brain was greater in the normal state than in the ictal state. The fluctuations of the approximate entropy before epileptic seizures observed in this study can form a good basis for further study on the prediction of seizures with nonlinear dynamics.展开更多
The automatic detection and identification of electroencephalogram waves play an important role in the prediction, diagnosis and treatment of epileptic seizures. In this study, a nonlinear dynamics index-approximate e...The automatic detection and identification of electroencephalogram waves play an important role in the prediction, diagnosis and treatment of epileptic seizures. In this study, a nonlinear dynamics index-approximate entropy and a support vector machine that has strong generalization ability were applied to classify electroencephalogram signals at epileptic interictal and ictal periods. Our aim was to verify whether approximate entropy waves can be effectively applied to the automatic real-time detection of epilepsy in the electroencephalogram, and to explore its generalization ability as a classifier trained using a nonlinear dynamics index. Four patients presenting with partial epileptic seizures were included in this study. They were all diagnosed with neocortex localized epilepsy and epileptic foci were clearly observed by electroencephalogram. The electroencephalogram data form the four involved patients were segmented and the characteristic values of each segment, that is, the approximate entropy, were extracted. The support vector machine classifier was constructed with the approximate entropy extracted from one epileptic case, and then electroencephalogram waves of the other three cases were classified, reaching a 93.33% accuracy rate. Our findings suggest that the use of approximate entropy allows the automatic real-time detection of electroencephalogram data in epileptic cases. The combination of approximate entropy and support vector machines shows good generalization ability for the classification of electroencephalogram signals for epilepsy.展开更多
The Na+-K+-Cl-cotransporter 1 and K+-Cl-cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells.Impaired chloride transport by these proteins is thought to be involved in the pathophysiologi...The Na+-K+-Cl-cotransporter 1 and K+-Cl-cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells.Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy.Imbalance in the relative expression of these two proteins can lead to a collapse of Cl-homeostasis,resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges.In this study,we investigated the expression of Na+-K+-Cl-cotransporter 1 and K+-Cl-cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy,using western blot analysis and immunohistochemistry.Compared with the histologically normal hippocampus,the sclerosed hippocampus showed increased Na+-K+-Cl-cotransporter 1 expression and decreased K+-Cl-cotransporter 2 expression,especially in CA2 and the dentate gyrus.The change was more prominent for the Na+-K+-Cl-cotransporter 1 than for the K+-Cl-cotransporter 2.These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis,contributing to the hyperexcitability underlying epileptic seizures.Changes in Na+-K+-Cl-cotransporter 1 expression seems to be the main contributor.Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.展开更多
In this work,the characterizations of Cu-SSZ-13 after hydrothermal aging(HTA)and thermal aging(TA)at different temperatures(750,800,and 850°C)are compared,and the differences between those two serious aged sample...In this work,the characterizations of Cu-SSZ-13 after hydrothermal aging(HTA)and thermal aging(TA)at different temperatures(750,800,and 850°C)are compared,and the differences between those two serious aged samples are analyzed.With this data,the effect of steam on catalysts deactivation during hydrothermal aging is analyzed.The TA at 750 and 800°C causes the dealumination and the agglomeration of Cu^(2+)ions to Cu O,resulting in the activity loss of Cu-SSZ-13.The presence of steam upon HTA at750 and 800°C aggravates the catalyst deactivation by increasing the Al detachment and the Cu^(2+)agglomeration.The structure and cupric state are almost the same in the Cu-SSZ-13 after TA and HTA at 850°C,respectively,indicating that the steam has little influence on the deactivation.The formation of CuAl_(2)O_(4) spinel is the primary reason for the deactivation after both HTA and TA at 850°C,probably attributed to the strong interaction between Cu^(2+)ions and framework Al sites at high temperatures.展开更多
Ore image segmentation is a key step in an ore grain size analysis based on image processing.The traditional segmentation methods do not deal with ore textures and shadows in ore images well Those methods often suffer...Ore image segmentation is a key step in an ore grain size analysis based on image processing.The traditional segmentation methods do not deal with ore textures and shadows in ore images well Those methods often suffer from under-segmentation and over-segmentation.In this article,in order to solve the problem,an ore image segmentation method based on U-Net is proposed.We adjust the structure of U-Net to speed up the processing,and we modify the loss function to enhance the generalization of the model.After the collection of the ore image,we design the annotation standard and train the network with the annotated image.Finally,the marked watershed algorithm is used to segment the adhesion area.The experimental results show that the proposed method has the characteristics of fast speed,strong robustness and high precision.It has great practical value to the actual ore grain statistical task.展开更多
As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-t...As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.展开更多
The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has seriously threatened global public health and caused huge economic losses.Omics studies of SARS-...The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has seriously threatened global public health and caused huge economic losses.Omics studies of SARS-CoV-2 can help understand the interaction between the virus and host,thereby providing a new perspective in guiding the intervention and treatment of the SARS-CoV-2 infection.Since large amount of SARS-CoV-2 omics data have been accumulated in public databases,this study aimed to identify key host factors involved in SARSCoV-2 infection through systematic integration of transcriptome and interactome data.By manually curating published studies,we obtained a comprehensive SARS-CoV-2-human protein-protein interactions(PPIs)network,comprising 3591 human proteins interacting with 31 SARS-CoV-2 viral proteins.Using the RobustRankAggregation method,we identified 123 multiple cell line common genes(CLCGs),of which 115 up-regulated CLCGs showed host enhanced innate immunity and chemotactic response signatures.Combined with network analysis,co-expression and functional enrichment analysis,we discovered four key host factors involved in SARS-CoV-2 infection:IFITM1,SERPINE1,DDX60,and TNFAIP2.Furthermore,SERPINE1 was found to facilitate SARSCoV-2 replication,and can alleviate the endoplasmic reticulum(ER)stress induced by ORF8 protein through interaction with ORF8.Our findings highlight the importance of systematic integration analysis in understanding SARS-CoV-2-human interactions and provide valuable insights for future research on potential therapeutic targets against SARS-CoV-2 infection.展开更多
Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective f...Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line therapy.Unfortunately,the development of drug resistance to sorafenib is becoming increasingly common.This study aims to identify factors contributing to resistance and ways to mitigate resistance.Recent studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression.This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.展开更多
Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play...Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.展开更多
Recent progress has been made on the synthesis and characterization of metal halide perovskite magic-sized clusters(PMSCs)with ABX_(3)composition(A=CH_(3)NH_(3)^(+)or Cs^(+),B=Pb^(2+),and X=Cl^(−),Br^(−),or I^(−)).How...Recent progress has been made on the synthesis and characterization of metal halide perovskite magic-sized clusters(PMSCs)with ABX_(3)composition(A=CH_(3)NH_(3)^(+)or Cs^(+),B=Pb^(2+),and X=Cl^(−),Br^(−),or I^(−)).However,their mechanism of growth and structure is still not well understood.In our effort to understand their structure and growth,we discovered that a new species can be formed without the CH_(3)NH_(3)^(+)component,which we name as molecular clusters(MCs).Specifically,CH_(3)NH_(3)PbBr_(3)PMSCs,with a characteristic absorption peak at 424 nm,are synthesized using PbBr_(2)and CH_(3)NH_(3)Br as precursors and butylamine(BTYA)and valeric acid(VA)as ligands,while MCs,with an absorption peak at 402 nm,are synthesized using solely PbBr_(2)and BTYA,without CH3NH3Br.Interestingly,PMSCs are converted spontaneously overtime into MCs.An isosbestic point in their electronic absorption spectra indicates a direct interplay between the PMSCs and MCs.Therefore,we suggest that the MCs are precursors to the PMSCs.From spectroscopic and extended X-ray absorption fine structure(EXAFS)results,we propose some tentative structural models for the MCs.The discovery of the MCs is critical to understanding the growth of PMSCs as well as larger perovskite quantum dots(PQDs)or nanocrystals(PNCs).展开更多
Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in...Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.展开更多
In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate i...In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.展开更多
Background:Voltage-gated sodium channels are the targets of many commonly used antiepileptic drugs.NaV1.6,encoded by Scn8a,increased in chronic mesial temporal epilepsy animal models and co-localized with Ankyrin-G,en...Background:Voltage-gated sodium channels are the targets of many commonly used antiepileptic drugs.NaV1.6,encoded by Scn8a,increased in chronic mesial temporal epilepsy animal models and co-localized with Ankyrin-G,encoded by Ank3.We hypothesized that inhibition of Ank3 transcription by siRNA decrease the expression of NaV1.6.Results:We characterized expression of the target genes in hippocampal neuron HT22 cells by Real time-PCR.The melt peak in the resolution curve of Scn1a,Scn8a and Ank3 were all unique.Ank3 transcription was interfered and the relative Ank3 mRNA levels of the three interfered groups compared to GAPDH were 0.89±0.13,0.52±0.07 and 0.26±0.05 while that of the negative control group was 1.01±0.08(P<0.05).When Ank3 transcription was inhibited by siRNA,the relative mRNA levels of Scn8a decreased in the three groups(0.91±0.09,0.33±0.06 and 0.25±0.05),compared to the negative control group(1.10±0.09).Tested by Western blotting,protein levels of ankyrinG and Nav1.6 decreased after ank3-siRNA.Ankyrin-G in negative control group,group1,group2 and group1+2 were 0.813±0.051,0.744±0.041,0.477±0.055 and 0.351±0.190 respectively(P<0.01)while Nav1.6 were 0.934±0.036,0.867±0.078,0.498±0.070 and 0.586±0.180(P<0.01).The quantity analysis of immunofluorescence showed significant decrease of ankyrin-G and Nav1.6(Student’s test,P=0.046 and 0.016 respectively).Conclusion:We therefore concluded that in HT22 cells the expression of Nav1.6 was down-regulated by Ank3 RNA interference.展开更多
基金Thisworkwas supported by the Shanghai Science and Technology Committee(No.22dz1204700)the NationalKeyR&D Program of China(Nos.2020YFA0803800 and 2017YFE0132200)+2 种基金the National Natural Science Foundation of China(Nos.82072510,21907034,21788102,21525417,and 51620105009)the Natural Science Foundation of Guangdong Province(Nos.2019B030301003 and 2016A030312002)the Innovation and Technology Commission of Hong Kong(No.ITC-CNERC14S01).
文摘Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation.The purpose of this study was to explore whether aggregation-induced emission luminogens(AIEgens)can be used for highly specific imaging of MSU crystals to assist in the diagnosis of gout.First,we developed a series of luminogens(i.e.,tetraphenyl ethylene(TPE)-NH_(2),TPE-2NH_(2),TPE-4NH_(2),TPE-COOH,TPE-2COOH,TPE-4COOH,and TPE-Ketoalkyne),each of which was then evenly mixed with MSU crystals.Next,optimal fluorescence imaging of each of the luminogens was characterized by a confocal laser scanning microscope(CLSM).This approach was used for imaging standard samples of MSU,hydroxyapatite(HAP)crystals,and mixed samples with 1:1 mass ratio of MSU/HAP.We also imaged samples from mouse models of acute gouty arthritis,HAP deposition disease,and comorbidities of interest.Subsequently,CLSM imaging results were compared with those of compensated polarized light microscopy,and we assessed the biosafety of TPE-Ketoalkyne in the RAW264.7 cell line.Finally,CLSM time series and three-dimensional imaging were performed on MSU crystal samples from human gouty synovial fluid and tophi.As a promising candidate for MSU crystal labeling,TPE-Ketoalkyne was found to detect MSU crystals accurately and rapidly in standard samples,animal samples,and human samples,and could precisely distinguish gout from HAP deposition disease.This work demonstrates that TPE-Ketoalkyne is suitable for highly specific and timely imaging of MSU crystals in gouty arthritis and may facilitate future research on MSU crystal-related diseases.
基金supported by the China Medical BoardOpen Competition Program(20-378)Peking University Third Hospital Fund for Returned Scholars(BYSYLXHG2020004)+1 种基金JX was supported by the Peking Union Medical College Fund for Informatization of Postgraduate Courses(2021YXX001)YLZ was supported by the Sichuan University Graduate Education Reform Project(GSSCU2021046)。
文摘BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.
基金supported by the National Natural Science Foundation of China, No.10671213 and 11101440the Natural Science Foundation of Guangdong ProvinceFundamental Research Funds for the Central Universities
文摘Electroencephalogram signals are time-varying complex electrophysiological signals. Existing studies show that approximate entropy, which is a nonlinear dynamics index, is not an ideal method for electroencephalogram analysis. Clinical electroencephalogram measurements usually contain electrical interference signals, creating additional challenges in terms of maintaining robustness of the analytic methods. There is an urgent need for a novel method of nonlinear dynamical analysis of the electroencephalogram that can characterize seizure-related changes in cerebral dynamics. The aim of this paper was to study the fluctuations of approximate entropy in preictal, ictal, and postictal electroencephalogram signals from a patient with absence seizures, and to improve the algorithm used to calculate the approximate entropy. The approximate entropy algorithm, especially our modified version, could accurately describe the dynamical changes of the brain during absence seizures. We could also demonstrate that the complexity of the brain was greater in the normal state than in the ictal state. The fluctuations of the approximate entropy before epileptic seizures observed in this study can form a good basis for further study on the prediction of seizures with nonlinear dynamics.
基金financially supported by the National Natural Science Foundation of China,No.61263011,81000554Program in Sun Yat-sen University supported by Fundamental Research Funds for the Central Universities,No.11ykpy07+1 种基金Natural Science Foundation of Guangdong Province,No.S2011010005309Innovation Fund of Xinjiang Medical University,No.XJC201209
文摘The automatic detection and identification of electroencephalogram waves play an important role in the prediction, diagnosis and treatment of epileptic seizures. In this study, a nonlinear dynamics index-approximate entropy and a support vector machine that has strong generalization ability were applied to classify electroencephalogram signals at epileptic interictal and ictal periods. Our aim was to verify whether approximate entropy waves can be effectively applied to the automatic real-time detection of epilepsy in the electroencephalogram, and to explore its generalization ability as a classifier trained using a nonlinear dynamics index. Four patients presenting with partial epileptic seizures were included in this study. They were all diagnosed with neocortex localized epilepsy and epileptic foci were clearly observed by electroencephalogram. The electroencephalogram data form the four involved patients were segmented and the characteristic values of each segment, that is, the approximate entropy, were extracted. The support vector machine classifier was constructed with the approximate entropy extracted from one epileptic case, and then electroencephalogram waves of the other three cases were classified, reaching a 93.33% accuracy rate. Our findings suggest that the use of approximate entropy allows the automatic real-time detection of electroencephalogram data in epileptic cases. The combination of approximate entropy and support vector machines shows good generalization ability for the classification of electroencephalogram signals for epilepsy.
基金supported by the Science and Technology Foundation of Guangdong Province,No.2008B060600063the National Natural Science Foundation of China,No. 81071050the Natural Science Foundation of Guangdong Province,No. S2011020005483
文摘The Na+-K+-Cl-cotransporter 1 and K+-Cl-cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells.Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy.Imbalance in the relative expression of these two proteins can lead to a collapse of Cl-homeostasis,resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges.In this study,we investigated the expression of Na+-K+-Cl-cotransporter 1 and K+-Cl-cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy,using western blot analysis and immunohistochemistry.Compared with the histologically normal hippocampus,the sclerosed hippocampus showed increased Na+-K+-Cl-cotransporter 1 expression and decreased K+-Cl-cotransporter 2 expression,especially in CA2 and the dentate gyrus.The change was more prominent for the Na+-K+-Cl-cotransporter 1 than for the K+-Cl-cotransporter 2.These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis,contributing to the hyperexcitability underlying epileptic seizures.Changes in Na+-K+-Cl-cotransporter 1 expression seems to be the main contributor.Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.
基金supported by the National Key Research and Development Program of China (2018YFC0214103)the National Natural Science Foundation of China (22006044)the Scientific Research Funds of Huaqiao University (605-50Y200270001)。
文摘In this work,the characterizations of Cu-SSZ-13 after hydrothermal aging(HTA)and thermal aging(TA)at different temperatures(750,800,and 850°C)are compared,and the differences between those two serious aged samples are analyzed.With this data,the effect of steam on catalysts deactivation during hydrothermal aging is analyzed.The TA at 750 and 800°C causes the dealumination and the agglomeration of Cu^(2+)ions to Cu O,resulting in the activity loss of Cu-SSZ-13.The presence of steam upon HTA at750 and 800°C aggravates the catalyst deactivation by increasing the Al detachment and the Cu^(2+)agglomeration.The structure and cupric state are almost the same in the Cu-SSZ-13 after TA and HTA at 850°C,respectively,indicating that the steam has little influence on the deactivation.The formation of CuAl_(2)O_(4) spinel is the primary reason for the deactivation after both HTA and TA at 850°C,probably attributed to the strong interaction between Cu^(2+)ions and framework Al sites at high temperatures.
基金This work was supported by The National Natural Science Foundation of China(Grant 61801019).
文摘Ore image segmentation is a key step in an ore grain size analysis based on image processing.The traditional segmentation methods do not deal with ore textures and shadows in ore images well Those methods often suffer from under-segmentation and over-segmentation.In this article,in order to solve the problem,an ore image segmentation method based on U-Net is proposed.We adjust the structure of U-Net to speed up the processing,and we modify the loss function to enhance the generalization of the model.After the collection of the ore image,we design the annotation standard and train the network with the annotated image.Finally,the marked watershed algorithm is used to segment the adhesion area.The experimental results show that the proposed method has the characteristics of fast speed,strong robustness and high precision.It has great practical value to the actual ore grain statistical task.
基金supported by the Areas of Excellence Scheme from University Grant Council of Hong Kong(AoE/M-402/20)the AO Foundation,Switzerland(AO-OCD Consortium TA1711481)+1 种基金the Theme-based Research Scheme from University Grant Council of Hong Kong(T13-402/17-N)the Mainland-Hong Kong Joint Funding Scheme of Innovation and Technology Fund:ITF MHKJFS(MHP/011/20).
文摘As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.
基金supported by the National Natural Science Foundation of China (32070678,82102371 and 31671371)the Emergency Key Program of Guangzhou Laboratory,grant no.EKPG21-12+3 种基金the Selfsupporting Program of Guangzhou Laboratory,Grant No.SRPG22-007,SRPG22-020the National Key Research and Development Program of China (2020YFC0840800)CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061)the National Key Research and Development Program of China (2021YFC2302000).
文摘The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has seriously threatened global public health and caused huge economic losses.Omics studies of SARS-CoV-2 can help understand the interaction between the virus and host,thereby providing a new perspective in guiding the intervention and treatment of the SARS-CoV-2 infection.Since large amount of SARS-CoV-2 omics data have been accumulated in public databases,this study aimed to identify key host factors involved in SARSCoV-2 infection through systematic integration of transcriptome and interactome data.By manually curating published studies,we obtained a comprehensive SARS-CoV-2-human protein-protein interactions(PPIs)network,comprising 3591 human proteins interacting with 31 SARS-CoV-2 viral proteins.Using the RobustRankAggregation method,we identified 123 multiple cell line common genes(CLCGs),of which 115 up-regulated CLCGs showed host enhanced innate immunity and chemotactic response signatures.Combined with network analysis,co-expression and functional enrichment analysis,we discovered four key host factors involved in SARS-CoV-2 infection:IFITM1,SERPINE1,DDX60,and TNFAIP2.Furthermore,SERPINE1 was found to facilitate SARSCoV-2 replication,and can alleviate the endoplasmic reticulum(ER)stress induced by ORF8 protein through interaction with ORF8.Our findings highlight the importance of systematic integration analysis in understanding SARS-CoV-2-human interactions and provide valuable insights for future research on potential therapeutic targets against SARS-CoV-2 infection.
基金supported by grants from the National Natural Science Key Foundation of China(grant No.81530048)the National Natural Youth Fund(grant No.81902485).
文摘Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line therapy.Unfortunately,the development of drug resistance to sorafenib is becoming increasingly common.This study aims to identify factors contributing to resistance and ways to mitigate resistance.Recent studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression.This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.
基金supported by the National Key R&D Program of China(Grant nos.2018YFC1311500(B.S.),2017YFC0907500(K.Y.)and 2018YFC0910400(K.Y.))National Science Foundation of China(NSFC)(Grant nos.81970679(B.S.),81500690(Y.W.),and 31671372(K.Y.))+3 种基金Natural Science Foundation of Shaanxi Province(2018JM70990(Y.W.))Key Research and Development Project of Shaanxi Province(Grant no.2017ZDXM-SF-060(B.S.))Fundamental Research Funds for the Central Universities(1191329875(Y.W.))the China Postdoctoral Science Foundation(224646(Y.W.)).
文摘Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.
基金supported by the NSF(CHE-1904547)for graduate students and chemicals and UCSC Committee on Research Special Research Grant for supplies and facility usagethe US DOE under contract no.DE-AC02-06CH11357 and the Canadian Light Source(CLS)and its funding partners.
文摘Recent progress has been made on the synthesis and characterization of metal halide perovskite magic-sized clusters(PMSCs)with ABX_(3)composition(A=CH_(3)NH_(3)^(+)or Cs^(+),B=Pb^(2+),and X=Cl^(−),Br^(−),or I^(−)).However,their mechanism of growth and structure is still not well understood.In our effort to understand their structure and growth,we discovered that a new species can be formed without the CH_(3)NH_(3)^(+)component,which we name as molecular clusters(MCs).Specifically,CH_(3)NH_(3)PbBr_(3)PMSCs,with a characteristic absorption peak at 424 nm,are synthesized using PbBr_(2)and CH_(3)NH_(3)Br as precursors and butylamine(BTYA)and valeric acid(VA)as ligands,while MCs,with an absorption peak at 402 nm,are synthesized using solely PbBr_(2)and BTYA,without CH3NH3Br.Interestingly,PMSCs are converted spontaneously overtime into MCs.An isosbestic point in their electronic absorption spectra indicates a direct interplay between the PMSCs and MCs.Therefore,we suggest that the MCs are precursors to the PMSCs.From spectroscopic and extended X-ray absorption fine structure(EXAFS)results,we propose some tentative structural models for the MCs.The discovery of the MCs is critical to understanding the growth of PMSCs as well as larger perovskite quantum dots(PQDs)or nanocrystals(PNCs).
基金supported in part by Theme-based Research Scheme of Hong Kong(No.T13-402/17 N)Health and Medical Research Fund of Hong Kong(15161441 and 18190481)+3 种基金Early Career Scheme of Hong Kong(No.24104517)Start-up fund at the Hong Kong Polytechnic UniversityNational Natural Science Foundation of China(81802152)Natural Science Foundation of Guangdong Province(2019A1515012224 and 2021A1515011204).
文摘Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.
基金supported by Theme-based Research Scheme(Ref No.T13-402/17-N)Collaborative Research Fund(C402617W)from the Research Grants Council of the Hong Kong Special Administrative Region,ChinaInnovation and Technology Fund(ITS/208/18FX)from the Innovation and Technology Commission of Hong Kong。
文摘In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.
基金the National Nature Science foundation(81000554)Guangdong Nature Science foundation(2018A030313345)the Science and Technology Foundation of Guangdong Province(2008B030301058).
文摘Background:Voltage-gated sodium channels are the targets of many commonly used antiepileptic drugs.NaV1.6,encoded by Scn8a,increased in chronic mesial temporal epilepsy animal models and co-localized with Ankyrin-G,encoded by Ank3.We hypothesized that inhibition of Ank3 transcription by siRNA decrease the expression of NaV1.6.Results:We characterized expression of the target genes in hippocampal neuron HT22 cells by Real time-PCR.The melt peak in the resolution curve of Scn1a,Scn8a and Ank3 were all unique.Ank3 transcription was interfered and the relative Ank3 mRNA levels of the three interfered groups compared to GAPDH were 0.89±0.13,0.52±0.07 and 0.26±0.05 while that of the negative control group was 1.01±0.08(P<0.05).When Ank3 transcription was inhibited by siRNA,the relative mRNA levels of Scn8a decreased in the three groups(0.91±0.09,0.33±0.06 and 0.25±0.05),compared to the negative control group(1.10±0.09).Tested by Western blotting,protein levels of ankyrinG and Nav1.6 decreased after ank3-siRNA.Ankyrin-G in negative control group,group1,group2 and group1+2 were 0.813±0.051,0.744±0.041,0.477±0.055 and 0.351±0.190 respectively(P<0.01)while Nav1.6 were 0.934±0.036,0.867±0.078,0.498±0.070 and 0.586±0.180(P<0.01).The quantity analysis of immunofluorescence showed significant decrease of ankyrin-G and Nav1.6(Student’s test,P=0.046 and 0.016 respectively).Conclusion:We therefore concluded that in HT22 cells the expression of Nav1.6 was down-regulated by Ank3 RNA interference.
