Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degra...Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s disease.These results may provide new insights on the underlying mechanism of Parkinson’s disease.展开更多
Plasma-activated water(PAW),as an extended form of cold atmospheric-pressure plasma,greatly expands the application of plasma-based technology.The biological effects of PAW are closely related to the aqueous reactive ...Plasma-activated water(PAW),as an extended form of cold atmospheric-pressure plasma,greatly expands the application of plasma-based technology.The biological effects of PAW are closely related to the aqueous reactive species,which can be regulated by the activation process.In this study,surface plasma-activated air(SAA)and a He+O_(2)plasma jet(Jet)were parallelly combined(the SAA+Jet combination)or sequentially combined(the SAA→Jet combination and the Jet→SAA combination)to prepare plasma-activated saline(PAS).The PAS activated by the combinations exhibited stronger bactericidal effects than that activated by the SAA or the Jet alone.The concentrations of H_(2)O_(2)and NO_(2)^(-)were higher in the PAS activated by the Jet→SAA combination,while ONOO^(-)concentrations were close in the three kinds of PAS and^(1)O_(2)concentrations were higher in the PAS activated by the SAA+Jet combination.The analysis of scavengers also demonstrated that H_(2)O_(2),^(1)O_(2),and ONOO^(-)in the PAS activated by the SAA+Jet combination,and^(1)O_(2)in the PAS activated by the Jet→SAA combination played critical roles in bactericidal effects.Further,the effective placement time of the three PAS varied,and the PAS activated by the Jet→SAA combination could also inactivate 2.6-log_(10)of MRSA cells after placement for more than 60 min.The regulation of reactive species in plasma-activated water via different combinations of plasma devices could improve the directional application of plasma-activated water in the biomedical field.展开更多
To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,es...To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.展开更多
Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have ...Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have excellent biocompatibility,electrical conductivity,surface hydrophilicity,mechanical properties and easy surface modification.However,at present,the stability of most MXenes needs to be improved,and more synthesis methods need to be explored.MXenes are good substrates for nerve cell regeneration and nerve reconstruction,which have broad application prospects in the repair of nervous system injury.Regarding the application of MXenes in neuroscience,mainly at the cellular level,the long-term in vivo biosafety and effects also need to be further explored.This review focuses on the progress of using MXenes in nerve regeneration over the last few years;discussing preparation of MXenes and their biocompatibility with different cells as well as the regulation by MXenes of nerve cell regeneration in two-dimensional and three-dimensional environments in vitro.MXenes have great potential in regulating the proliferation,differentiation,and maturation of nerve cells and in promoting regeneration and recovery after nerve injury.In addition,this review also presents the main challenges during optimization processes,such as the preparation of stable MXenes and long-term in vivo biosafety,and further discusses future directions in neural tissue engineering.展开更多
Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides minin...Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data.In this study,we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences.By functional annotation and amino acid composition analysis,we have discovered various genes related to signal transduction,and 16 genes related to longevity.We have also found vast variety of functional peptides through protein coding sequence(CDS)analysis by comparing the data obtained with the functional peptide database.Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis,suggesting that our approach is reliable.This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat,thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.展开更多
Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor a...Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.展开更多
Schwann cell proliferation,migration and remyelination of regenerating axons contribute to regeneration after peripheral nervous system injury.Lithium promotes remyelination by Schwann cells and improves peripheral ne...Schwann cell proliferation,migration and remyelination of regenerating axons contribute to regeneration after peripheral nervous system injury.Lithium promotes remyelination by Schwann cells and improves peripheral nerve regeneration.However,whether lithium modulates other phenotypes of Schwann cells,especially their proliferation and migration remains elusive.In the current study,primary Schwann cells from rat sciatic nerve stumps were cultured and exposed to 0,5,10,15,or 30 mM lithium chloride(LiCl)for 24 hours.The effects of LiCl on Schwann cell proliferation and migration were examined using the Cell Counting Kit-8,5-ethynyl-2′-deoxyuridine,Transwell and wound healing assays.Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays showed that 5,10,15,and 30 mM LiCl significantly increased the viability and proliferation rate of Schwann cells.Transwell-based migration assays and wound healing assays showed that 10,15,and 30 mM LiCl suppressed the migratory ability of Schwann cells.Furthermore,the effects of LiCl on the proliferation and migration phenotypes of Schwann cells were mostly dose-dependent.These data indicate that lithium treatment significantly promotes the proliferation and inhibits the migratory ability of Schwann cells.This conclusion will inform strategies to promote the repair and regeneration of peripheral nerves.All of the animal experiments in this study were ethically approved by the Administration Committee of Experimental Animal Center of Nantong University,China(approval No.20170320-017)on March 2,2017.展开更多
The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 ...The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.展开更多
Cardiomyopathies represent the most common clinical and genetic heterogeneous group of diseases that affect the heart function.Though progress has been made to elucidate the process,molecular mechanisms of different c...Cardiomyopathies represent the most common clinical and genetic heterogeneous group of diseases that affect the heart function.Though progress has been made to elucidate the process,molecular mechanisms of different classes of cardiomyopathies remain elusive.This paper aims to describe the similarities and differences in molecular features of dilated cardiomyopathy(DCM)and ischemic cardiomyopathy(ICM).We firstly detected the co-expressed modules using the weighted gene co-expression network analysis(WGCNA).Significant modules associated with DCM/ICM were identified by the Pearson correlation coefficient(PCC)between the modules and the phenotype of DCM/ICM.The differentially expressed genes in the modules were selected to perform functional enrichment.The potential transcription factors(TFs)prediction was conducted for transcription regulation of hub genes.Apoptosis and cardiac conduction were perturbed in DCM and ICM,respectively.TFs demonstrated that the biomarkers and the transcription regulations in DCM and ICM were different,which helps make more accurate discrimination between them at molecular levels.In conclusion,comprehensive analyses of the molecular features may advance our understanding of DCM and ICM causes and progression.Thus,this understanding may promote the development of innovative diagnoses and treatments.展开更多
Mitochondrial genomes(mitogenomes)in frogs are essential for reconstructing the phylogenetic relationships and shedding light on the molecular evolution in these animals.However,there are only seven complete Rhacophor...Mitochondrial genomes(mitogenomes)in frogs are essential for reconstructing the phylogenetic relationships and shedding light on the molecular evolution in these animals.However,there are only seven complete Rhacophoridae genomes that have been reported to date.In this paper,two complete mitogenomes of the Chinese whipping frog(Zhangixalus chenfui)and Emei tree frog(Z.omeimontis)were described,each of which was 20520 and 19782 bp in size,and had A+T contents of 64.26%and 63.83%.The two mitogenomes each included two non-coding control region(D-loop,CR),two ribosomal RNA genes(rRNAs),13 protein-coding genes(PCGs),and 22 transfer RNA genes(tRNAs),and it was found that the mitogenome of Z.chenfui also includes three tandem tRNAMet gene sequences.A typical clover-leaf structure was found for all tRNAs except for tRNASer1(AGN),which showed a reduced DHU arm.The putative D-loop region contains multiple types of tandem repeats regions.Both of these two mitogenomes showed similar pattern of gene rearrangement(tRNA-Ser-ND6-tRNA-Glu-CytbCR1-ND5-CR2-tRNA-Thr-tRNA-Leu-tRNA-Pro).Additionally,three consecutive tRNAMet genes were found for the first time in Z.chenfui,a species in the Rhacophoridae family.For all phylogenetic analyses,which were based on 13 protein-coding genes from 91 Ranoidea mitogenomes,the same phylogenetic trees were observed using either maximum likelihood or Bayesian approaches.These results suggest that the phylogenetic hypotheses for the Ranoidea(including Rhacophoridae,Mantellidae,Ranidae and Dicroglossidae)derived from these mitogenomic data could provide substantiation for the relationships of(Dicroglossidae(Ranidae,(Mantellidae,Rhacophoridae))),and support the presence of a monophyletic group in four families.Moreover,Z.omeimontis and Z.dennysi were found to cluster on the same branch,indicating that they were more closely related as a group.This group may in turn form sister groups with Z.arboreus and Z.schlegelii.However,Z.chenfui is located on the base of other species in the genera.Increased mitogenome sampling should be conducted to provide a more satisfactory resolution to the phylogeny of the Rhacophorus,Rhacophoridae,and Mantellidae.展开更多
Developmental motifs in neurodegeneration:Neurodegeneration,the prominent feature of neurodegenerative disease,is characterized by the progressive and selective loss of neuronal function.As some of the pathologies cau...Developmental motifs in neurodegeneration:Neurodegeneration,the prominent feature of neurodegenerative disease,is characterized by the progressive and selective loss of neuronal function.As some of the pathologies caused by neurodegeneration may be irreversible,early intervention will be required for the treatments that aim to slow or halt the manifestation of these diseases.Traditionally,neurodegeneration evokes the idea of a progressive decline of brain function.展开更多
Objective Programmed cell death 6(PDCD6), a Ca~(2+)-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatoc...Objective Programmed cell death 6(PDCD6), a Ca~(2+)-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas(HCCs).Methods The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium(MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.Results The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.Conclusion PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.展开更多
During marine missions,AUVs are susceptible to external disturbances,such as obstacles,ocean currents,etc.,which can easily cause mission failure or disconnection.In this paper,considering the strong nonlinearities,ex...During marine missions,AUVs are susceptible to external disturbances,such as obstacles,ocean currents,etc.,which can easily cause mission failure or disconnection.In this paper,considering the strong nonlinearities,external disturbances and obstacles,the kinematic and dynamic model of bioinspired Spherical Underwater Robot(SUR)was described.Subsequently,the waypoints-based trajectory tracking with obstacles and uncertainties was proposed for SUR to guarantee its safety and stability.Next,the Lyapunov theory was adopted to verify the stability and the Slide Mode Control(SMC)method is used to verify the robustness of the control system.In addition,a series of simulations were conducted to evaluate the effectiveness of proposed control strategy.Some tests,including path-following,static and moving obstacle avoidance were performed which verified the feasibility,robustness and effectiveness of the designed control scheme.Finally,a series of experiments in real environment were performed to verify the performance of the control strategy.The simulation and experimental results of the study supplied clues to the improvement of the path following capability and multi-obstacle avoidance of AUVs.展开更多
Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vit...Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.展开更多
Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substan...Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substance,cyclic opine:cycloalanopine.This study aimed to investigate whether LR could ameliorate dextran sulfate sodium-induced UC in mice via modulating intestinal microbiota using fecal microbiota transplantation(FMT)experiment.The results showed that both LR and FMT attenuated UC as evidenced by 1)alleviating disease activity index and colonic pathology;2)up-regulating MUCs and tight junction proteins;3)increasing oxidative mediators and decreasing antioxidant mediators;4)down-regulating proinflammatory cytokines and chemokines.These results were mainly attributable to the microbiota-regulating effect of LR,including increasing beneficial bacteria(like Akkermansia)and its related SCFAs,while decreasing harmful bacteria(like Proteobacteria)and its related LPS,thereby suppressing the hyperactivation of TLR4/NF-κB pathway.Consequently,LR can alleviate UC and is a potential dietary supplement to attenuate UC.展开更多
BACKGROUND Deep learning provides an efficient automatic image recognition method for small bowel(SB)capsule endoscopy(CE)that can assist physicians in diagnosis.However,the existing deep learning models present some ...BACKGROUND Deep learning provides an efficient automatic image recognition method for small bowel(SB)capsule endoscopy(CE)that can assist physicians in diagnosis.However,the existing deep learning models present some unresolved challenges.AIM To propose a novel and effective classification and detection model to automatically identify various SB lesions and their bleeding risks,and label the lesions accurately so as to enhance the diagnostic efficiency of physicians and the ability to identify high-risk bleeding groups.METHODS The proposed model represents a two-stage method that combined image classification with object detection.First,we utilized the improved ResNet-50 classification model to classify endoscopic images into SB lesion images,normal SB mucosa images,and invalid images.Then,the improved YOLO-V5 detection model was utilized to detect the type of lesion and its risk of bleeding,and the location of the lesion was marked.We constructed training and testing sets and compared model-assisted reading with physician reading.RESULTS The accuracy of the model constructed in this study reached 98.96%,which was higher than the accuracy of other systems using only a single module.The sensitivity,specificity,and accuracy of the model-assisted reading detection of all images were 99.17%,99.92%,and 99.86%,which were significantly higher than those of the endoscopists’diagnoses.The image processing time of the model was 48 ms/image,and the image processing time of the physicians was 0.40±0.24 s/image(P<0.001).CONCLUSION The deep learning model of image classification combined with object detection exhibits a satisfactory diagnostic effect on a variety of SB lesions and their bleeding risks in CE images,which enhances the diagnostic efficiency of physicians and improves the ability of physicians to identify high-risk bleeding groups.展开更多
Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, trad...Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.展开更多
Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the pr...Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.展开更多
Artificial Intelligence(AI)is being increasingly used for diagnosing Vision-Threatening Diabetic Retinopathy(VTDR),which is a leading cause of visual impairment and blindness worldwide.However,previous automated VTDR ...Artificial Intelligence(AI)is being increasingly used for diagnosing Vision-Threatening Diabetic Retinopathy(VTDR),which is a leading cause of visual impairment and blindness worldwide.However,previous automated VTDR detection methods have mainly relied on manual feature extraction and classification,leading to errors.This paper proposes a novel VTDR detection and classification model that combines different models through majority voting.Our proposed methodology involves preprocessing,data augmentation,feature extraction,and classification stages.We use a hybrid convolutional neural network-singular value decomposition(CNN-SVD)model for feature extraction and selection and an improved SVM-RBF with a Decision Tree(DT)and K-Nearest Neighbor(KNN)for classification.We tested our model on the IDRiD dataset and achieved an accuracy of 98.06%,a sensitivity of 83.67%,and a specificity of 100%for DR detection and evaluation tests,respectively.Our proposed approach outperforms baseline techniques and provides a more robust and accurate method for VTDR detection.展开更多
Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradab...Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats. Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds-and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells(regenerating nerve fibers) and less glial fibrillary acidic protein-immunoreactive cells(astrocytic scar tissue) were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue, and as such, is more suitable to help the repair of spinal cord injury.展开更多
基金supported by the National Natural Science Foundation of China,Nos.31871039 and 32170962(to MSH).
文摘Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s disease.These results may provide new insights on the underlying mechanism of Parkinson’s disease.
基金supported by National Natural Science Foundation of China(No.51977174)。
文摘Plasma-activated water(PAW),as an extended form of cold atmospheric-pressure plasma,greatly expands the application of plasma-based technology.The biological effects of PAW are closely related to the aqueous reactive species,which can be regulated by the activation process.In this study,surface plasma-activated air(SAA)and a He+O_(2)plasma jet(Jet)were parallelly combined(the SAA+Jet combination)or sequentially combined(the SAA→Jet combination and the Jet→SAA combination)to prepare plasma-activated saline(PAS).The PAS activated by the combinations exhibited stronger bactericidal effects than that activated by the SAA or the Jet alone.The concentrations of H_(2)O_(2)and NO_(2)^(-)were higher in the PAS activated by the Jet→SAA combination,while ONOO^(-)concentrations were close in the three kinds of PAS and^(1)O_(2)concentrations were higher in the PAS activated by the SAA+Jet combination.The analysis of scavengers also demonstrated that H_(2)O_(2),^(1)O_(2),and ONOO^(-)in the PAS activated by the SAA+Jet combination,and^(1)O_(2)in the PAS activated by the Jet→SAA combination played critical roles in bactericidal effects.Further,the effective placement time of the three PAS varied,and the PAS activated by the Jet→SAA combination could also inactivate 2.6-log_(10)of MRSA cells after placement for more than 60 min.The regulation of reactive species in plasma-activated water via different combinations of plasma devices could improve the directional application of plasma-activated water in the biomedical field.
基金the National Natural Science Foundation of China(81871426,81871430,82260359,U22A20303)Hebei Provincial Natural Science Foundation(H2020206263,H2020206625)STI2030-Major Projects Program(2022ZD0214500).
文摘To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.
基金supported by grants from the National Key R&D Program of China,Nos.2021YFA1101300,2021YFA1101803,2020YFA0112503the National Natural Science Foundation of China,Nos.82030029,81970882,92149304Science and Technology Department of Sichuan Province,No.2021YFS0371(all to RC)。
文摘Transition metal carbides and nitrides(MXenes)are crystal nanomaterials with a number of surface functional groups such as fluorine,hydroxyl,and oxygen,which can be used as carriers for proteins and drugs.MXenes have excellent biocompatibility,electrical conductivity,surface hydrophilicity,mechanical properties and easy surface modification.However,at present,the stability of most MXenes needs to be improved,and more synthesis methods need to be explored.MXenes are good substrates for nerve cell regeneration and nerve reconstruction,which have broad application prospects in the repair of nervous system injury.Regarding the application of MXenes in neuroscience,mainly at the cellular level,the long-term in vivo biosafety and effects also need to be further explored.This review focuses on the progress of using MXenes in nerve regeneration over the last few years;discussing preparation of MXenes and their biocompatibility with different cells as well as the regulation by MXenes of nerve cell regeneration in two-dimensional and three-dimensional environments in vitro.MXenes have great potential in regulating the proliferation,differentiation,and maturation of nerve cells and in promoting regeneration and recovery after nerve injury.In addition,this review also presents the main challenges during optimization processes,such as the preparation of stable MXenes and long-term in vivo biosafety,and further discusses future directions in neural tissue engineering.
基金funded by Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)。
文摘Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data.In this study,we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences.By functional annotation and amino acid composition analysis,we have discovered various genes related to signal transduction,and 16 genes related to longevity.We have also found vast variety of functional peptides through protein coding sequence(CDS)analysis by comparing the data obtained with the functional peptide database.Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis,suggesting that our approach is reliable.This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat,thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.
基金National Key R&D Program of China(2022YFA1103200,2017YFA0106400,2021YFA1100900)Ministry of Science and Technology of China(2020YFC2002804)+3 种基金National Natural Science Foundation of China(91749124,81772389,82070108)Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004)Fundamental Research Funds for the Central Universities(22120190149 and kx0200020173386)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai。
文摘Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
基金supported by the National Natural Science Foundation of China,No.81970820(to HX)
文摘Schwann cell proliferation,migration and remyelination of regenerating axons contribute to regeneration after peripheral nervous system injury.Lithium promotes remyelination by Schwann cells and improves peripheral nerve regeneration.However,whether lithium modulates other phenotypes of Schwann cells,especially their proliferation and migration remains elusive.In the current study,primary Schwann cells from rat sciatic nerve stumps were cultured and exposed to 0,5,10,15,or 30 mM lithium chloride(LiCl)for 24 hours.The effects of LiCl on Schwann cell proliferation and migration were examined using the Cell Counting Kit-8,5-ethynyl-2′-deoxyuridine,Transwell and wound healing assays.Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays showed that 5,10,15,and 30 mM LiCl significantly increased the viability and proliferation rate of Schwann cells.Transwell-based migration assays and wound healing assays showed that 10,15,and 30 mM LiCl suppressed the migratory ability of Schwann cells.Furthermore,the effects of LiCl on the proliferation and migration phenotypes of Schwann cells were mostly dose-dependent.These data indicate that lithium treatment significantly promotes the proliferation and inhibits the migratory ability of Schwann cells.This conclusion will inform strategies to promote the repair and regeneration of peripheral nerves.All of the animal experiments in this study were ethically approved by the Administration Committee of Experimental Animal Center of Nantong University,China(approval No.20170320-017)on March 2,2017.
基金supported by the National Key Research and Development Project of China,Nos.2017YFA0104100(to JL),2017YFA0701304(to HX)National Natural Science Foundation of China Nos.81970820(to HX),31930068(to JL)。
文摘The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.
基金supported by the National Natural Science Foundation of China under Grants No.61720106004 and No.61872405the Key R&D Project of Sichuan Province,China under Grants No.20ZDYF2772 and No.2020YFS0243.
文摘Cardiomyopathies represent the most common clinical and genetic heterogeneous group of diseases that affect the heart function.Though progress has been made to elucidate the process,molecular mechanisms of different classes of cardiomyopathies remain elusive.This paper aims to describe the similarities and differences in molecular features of dilated cardiomyopathy(DCM)and ischemic cardiomyopathy(ICM).We firstly detected the co-expressed modules using the weighted gene co-expression network analysis(WGCNA).Significant modules associated with DCM/ICM were identified by the Pearson correlation coefficient(PCC)between the modules and the phenotype of DCM/ICM.The differentially expressed genes in the modules were selected to perform functional enrichment.The potential transcription factors(TFs)prediction was conducted for transcription regulation of hub genes.Apoptosis and cardiac conduction were perturbed in DCM and ICM,respectively.TFs demonstrated that the biomarkers and the transcription regulations in DCM and ICM were different,which helps make more accurate discrimination between them at molecular levels.In conclusion,comprehensive analyses of the molecular features may advance our understanding of DCM and ICM causes and progression.Thus,this understanding may promote the development of innovative diagnoses and treatments.
基金This work was supported by the National Natural Science Foundation of China(No.32270457)the Natural Science Foundation Province of Science and Technology Department of Sichuan Probince(No.2023NSFSC0206)+1 种基金the Research Project of Ecological Security and Protection Key Laboratory of Sichuan Province(No.ESP2003)the Research Project of Education Office Project of Sichuan Province(No.18ZA0261).
文摘Mitochondrial genomes(mitogenomes)in frogs are essential for reconstructing the phylogenetic relationships and shedding light on the molecular evolution in these animals.However,there are only seven complete Rhacophoridae genomes that have been reported to date.In this paper,two complete mitogenomes of the Chinese whipping frog(Zhangixalus chenfui)and Emei tree frog(Z.omeimontis)were described,each of which was 20520 and 19782 bp in size,and had A+T contents of 64.26%and 63.83%.The two mitogenomes each included two non-coding control region(D-loop,CR),two ribosomal RNA genes(rRNAs),13 protein-coding genes(PCGs),and 22 transfer RNA genes(tRNAs),and it was found that the mitogenome of Z.chenfui also includes three tandem tRNAMet gene sequences.A typical clover-leaf structure was found for all tRNAs except for tRNASer1(AGN),which showed a reduced DHU arm.The putative D-loop region contains multiple types of tandem repeats regions.Both of these two mitogenomes showed similar pattern of gene rearrangement(tRNA-Ser-ND6-tRNA-Glu-CytbCR1-ND5-CR2-tRNA-Thr-tRNA-Leu-tRNA-Pro).Additionally,three consecutive tRNAMet genes were found for the first time in Z.chenfui,a species in the Rhacophoridae family.For all phylogenetic analyses,which were based on 13 protein-coding genes from 91 Ranoidea mitogenomes,the same phylogenetic trees were observed using either maximum likelihood or Bayesian approaches.These results suggest that the phylogenetic hypotheses for the Ranoidea(including Rhacophoridae,Mantellidae,Ranidae and Dicroglossidae)derived from these mitogenomic data could provide substantiation for the relationships of(Dicroglossidae(Ranidae,(Mantellidae,Rhacophoridae))),and support the presence of a monophyletic group in four families.Moreover,Z.omeimontis and Z.dennysi were found to cluster on the same branch,indicating that they were more closely related as a group.This group may in turn form sister groups with Z.arboreus and Z.schlegelii.However,Z.chenfui is located on the base of other species in the genera.Increased mitogenome sampling should be conducted to provide a more satisfactory resolution to the phylogeny of the Rhacophorus,Rhacophoridae,and Mantellidae.
文摘Developmental motifs in neurodegeneration:Neurodegeneration,the prominent feature of neurodegenerative disease,is characterized by the progressive and selective loss of neuronal function.As some of the pathologies caused by neurodegeneration may be irreversible,early intervention will be required for the treatments that aim to slow or halt the manifestation of these diseases.Traditionally,neurodegeneration evokes the idea of a progressive decline of brain function.
基金supported by Shanxi Province Science Foundation for Youths [20210302124668]Science Research Start-up Fund for Doctor of Shanxi Province [SD2115]+1 种基金Science Research Start-up Fund for Doctor of Shanxi Medical University [XD2021]Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi[2021L215]。
文摘Objective Programmed cell death 6(PDCD6), a Ca~(2+)-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas(HCCs).Methods The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium(MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.Results The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.Conclusion PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.
基金supported in part by the National Natural Science Foundation of China under Grant 61703305,in part by the National High TechResearch and Development Program(863 Program)of China under Grant 2015AA043202+3 种基金in part by the Japan Society for the Promotion of Science(SPS)KAKENHI under Grant 15K2120in part by the Key Research Program of the Natural Science Foundation of Tianjin under Grant 18JCZDJC38500in part by the Innovative Cooperation Project of Tianjin Scientific and Technological Support under Grant 18PTZWHZ00090in part by the China Scholarship Council(CSC)for his doctoral research at Kagawa University under Grant 202208050040.
文摘During marine missions,AUVs are susceptible to external disturbances,such as obstacles,ocean currents,etc.,which can easily cause mission failure or disconnection.In this paper,considering the strong nonlinearities,external disturbances and obstacles,the kinematic and dynamic model of bioinspired Spherical Underwater Robot(SUR)was described.Subsequently,the waypoints-based trajectory tracking with obstacles and uncertainties was proposed for SUR to guarantee its safety and stability.Next,the Lyapunov theory was adopted to verify the stability and the Slide Mode Control(SMC)method is used to verify the robustness of the control system.In addition,a series of simulations were conducted to evaluate the effectiveness of proposed control strategy.Some tests,including path-following,static and moving obstacle avoidance were performed which verified the feasibility,robustness and effectiveness of the designed control scheme.Finally,a series of experiments in real environment were performed to verify the performance of the control strategy.The simulation and experimental results of the study supplied clues to the improvement of the path following capability and multi-obstacle avoidance of AUVs.
基金Fundings supported by grants from the National Key Research and Development Program of China(Grant No.2017YFA0103902,2018YFA0800300,2019YFA0801900,2019YFA0111400)National Natural Science Foundation of China(Grant No.31771283,91749104,31971074)+3 种基金the Fundamental Research Funds for the Central Universities of Tongji University(No.22120190210)Innovative Research Team of High-Level Local Universities in Shanghai(No.SSMUZDCX20180700)Key Laboratory Program of the Education Commission of Shanghai Municipality(No.DSYS14005)the Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee(No.18140901300).
文摘Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.
基金supported by the National Natural Science Foundation of China(32001652)Chinese Universities Scientific Fund(2452018062)Keypoint Research and Invention Program of Shannxi Province(2021ZDLNY05-06)。
文摘Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substance,cyclic opine:cycloalanopine.This study aimed to investigate whether LR could ameliorate dextran sulfate sodium-induced UC in mice via modulating intestinal microbiota using fecal microbiota transplantation(FMT)experiment.The results showed that both LR and FMT attenuated UC as evidenced by 1)alleviating disease activity index and colonic pathology;2)up-regulating MUCs and tight junction proteins;3)increasing oxidative mediators and decreasing antioxidant mediators;4)down-regulating proinflammatory cytokines and chemokines.These results were mainly attributable to the microbiota-regulating effect of LR,including increasing beneficial bacteria(like Akkermansia)and its related SCFAs,while decreasing harmful bacteria(like Proteobacteria)and its related LPS,thereby suppressing the hyperactivation of TLR4/NF-κB pathway.Consequently,LR can alleviate UC and is a potential dietary supplement to attenuate UC.
基金The Shanxi Provincial Administration of Traditional Chinese Medicine,No.2023ZYYDA2005.
文摘BACKGROUND Deep learning provides an efficient automatic image recognition method for small bowel(SB)capsule endoscopy(CE)that can assist physicians in diagnosis.However,the existing deep learning models present some unresolved challenges.AIM To propose a novel and effective classification and detection model to automatically identify various SB lesions and their bleeding risks,and label the lesions accurately so as to enhance the diagnostic efficiency of physicians and the ability to identify high-risk bleeding groups.METHODS The proposed model represents a two-stage method that combined image classification with object detection.First,we utilized the improved ResNet-50 classification model to classify endoscopic images into SB lesion images,normal SB mucosa images,and invalid images.Then,the improved YOLO-V5 detection model was utilized to detect the type of lesion and its risk of bleeding,and the location of the lesion was marked.We constructed training and testing sets and compared model-assisted reading with physician reading.RESULTS The accuracy of the model constructed in this study reached 98.96%,which was higher than the accuracy of other systems using only a single module.The sensitivity,specificity,and accuracy of the model-assisted reading detection of all images were 99.17%,99.92%,and 99.86%,which were significantly higher than those of the endoscopists’diagnoses.The image processing time of the model was 48 ms/image,and the image processing time of the physicians was 0.40±0.24 s/image(P<0.001).CONCLUSION The deep learning model of image classification combined with object detection exhibits a satisfactory diagnostic effect on a variety of SB lesions and their bleeding risks in CE images,which enhances the diagnostic efficiency of physicians and improves the ability of physicians to identify high-risk bleeding groups.
基金the National Natural Science Foundation of China(81973221)National Natural Science Foundation for Young Scientists of China(81603647)+2 种基金the Women and Children Health Talent Project of Jiangsu Province(FRC201785)the Chinese Clinical Medicine Innovation Center of Obstetrics,Gynecology,and Reproduction in Jiangsu Province(ZX202102)the Women and Children Health Science Foundation of Jiangsu Province(F202206).
文摘Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.
基金supported by the STI 2030-Major Projects 2022ZD0208500(to DY)the National Natural Science Foundation of China,Nos.82072011(to YX),82121003(to DY),82271120(to YS)+2 种基金Sichuan Science and Technology Program,No.2022ZYD0066(to YS)a grant from Chinese Academy of Medical Science,No.2019-12M-5-032(to YS)the Fundamental Research Funds for the Central Universities,No.ZYGX2021YGLH219(to KC)。
文摘Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.
基金This research was funded by the National Natural Science Foundation of China(Nos.71762010,62262019,62162025,61966013,12162012)the Hainan Provincial Natural Science Foundation of China(Nos.823RC488,623RC481,620RC603,621QN241,620RC602,121RC536)+1 种基金the Haikou Science and Technology Plan Project of China(No.2022-016)the Project supported by the Education Department of Hainan Province,No.Hnky2021-23.
文摘Artificial Intelligence(AI)is being increasingly used for diagnosing Vision-Threatening Diabetic Retinopathy(VTDR),which is a leading cause of visual impairment and blindness worldwide.However,previous automated VTDR detection methods have mainly relied on manual feature extraction and classification,leading to errors.This paper proposes a novel VTDR detection and classification model that combines different models through majority voting.Our proposed methodology involves preprocessing,data augmentation,feature extraction,and classification stages.We use a hybrid convolutional neural network-singular value decomposition(CNN-SVD)model for feature extraction and selection and an improved SVM-RBF with a Decision Tree(DT)and K-Nearest Neighbor(KNN)for classification.We tested our model on the IDRiD dataset and achieved an accuracy of 98.06%,a sensitivity of 83.67%,and a specificity of 100%for DR detection and evaluation tests,respectively.Our proposed approach outperforms baseline techniques and provides a more robust and accurate method for VTDR detection.
基金supported by the National Natural Science Foundation of China,No.81671243 and 81373429
文摘Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats. Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds-and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells(regenerating nerve fibers) and less glial fibrillary acidic protein-immunoreactive cells(astrocytic scar tissue) were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue, and as such, is more suitable to help the repair of spinal cord injury.
