Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)iso...Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.展开更多
Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are...The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.展开更多
Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular funct...Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.展开更多
Transformer-based models have facilitated significant advances in object detection.However,their extensive computational consumption and suboptimal detection of dense small objects curtail their applicability in unman...Transformer-based models have facilitated significant advances in object detection.However,their extensive computational consumption and suboptimal detection of dense small objects curtail their applicability in unmanned aerial vehicle(UAV)imagery.Addressing these limitations,we propose a hybrid transformer-based detector,H-DETR,and enhance it for dense small objects,leading to an accurate and efficient model.Firstly,we introduce a hybrid transformer encoder,which integrates a convolutional neural network-based cross-scale fusion module with the original encoder to handle multi-scale feature sequences more efficiently.Furthermore,we propose two novel strategies to enhance detection performance without incurring additional inference computation.Query filter is designed to cope with the dense clustering inherent in drone-captured images by counteracting similar queries with a training-aware non-maximum suppression.Adversarial denoising learning is a novel enhancement method inspired by adversarial learning,which improves the detection of numerous small targets by counteracting the effects of artificial spatial and semantic noise.Extensive experiments on the VisDrone and UAVDT datasets substantiate the effectiveness of our approach,achieving a significant improvement in accuracy with a reduction in computational complexity.Our method achieves 31.9%and 21.1%AP on the VisDrone and UAVDT datasets,respectively,and has a faster inference speed,making it a competitive model in UAV image object detection.展开更多
To address the challenges of high complexity,poor real-time performance,and low detection rates for small target vehicles in existing vehicle object detection algorithms,this paper proposes a real-time lightweight arc...To address the challenges of high complexity,poor real-time performance,and low detection rates for small target vehicles in existing vehicle object detection algorithms,this paper proposes a real-time lightweight architecture based on You Only Look Once(YOLO)v5m.Firstly,a lightweight upsampling operator called Content-Aware Reassembly of Features(CARAFE)is introduced in the feature fusion layer of the network to maximize the extraction of deep-level features for small target vehicles,reducing the missed detection rate and false detection rate.Secondly,a new prediction layer for tiny targets is added,and the feature fusion network is redesigned to enhance the detection capability for small targets.Finally,this paper applies L1 regularization to train the improved network,followed by pruning and fine-tuning operations to remove redundant channels,reducing computational and parameter complexity and enhancing the detection efficiency of the network.Training is conducted on the VisDrone2019-DET dataset.The experimental results show that the proposed algorithmreduces parameters and computation by 63.8% and 65.8%,respectively.The average detection accuracy improves by 5.15%,and the detection speed reaches 47 images per second,satisfying real-time requirements.Compared with existing approaches,including YOLOv5m and classical vehicle detection algorithms,our method achieves higher accuracy and faster speed for real-time detection of small target vehicles in edge computing.展开更多
BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metas...BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.展开更多
Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune chec...Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.展开更多
Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension a...Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.展开更多
Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)...Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.展开更多
Effective small object detection is crucial in various applications including urban intelligent transportation and pedestrian detection.However,small objects are difficult to detect accurately because they contain les...Effective small object detection is crucial in various applications including urban intelligent transportation and pedestrian detection.However,small objects are difficult to detect accurately because they contain less information.Many current methods,particularly those based on Feature Pyramid Network(FPN),address this challenge by leveraging multi-scale feature fusion.However,existing FPN-based methods often suffer from inadequate feature fusion due to varying resolutions across different layers,leading to suboptimal small object detection.To address this problem,we propose the Two-layerAttention Feature Pyramid Network(TA-FPN),featuring two key modules:the Two-layer Attention Module(TAM)and the Small Object Detail Enhancement Module(SODEM).TAM uses the attention module to make the network more focused on the semantic information of the object and fuse it to the lower layer,so that each layer contains similar semantic information,to alleviate the problem of small object information being submerged due to semantic gaps between different layers.At the same time,SODEM is introduced to strengthen the local features of the object,suppress background noise,enhance the information details of the small object,and fuse the enhanced features to other feature layers to ensure that each layer is rich in small object information,to improve small object detection accuracy.Our extensive experiments on challenging datasets such as Microsoft Common Objects inContext(MSCOCO)and Pattern Analysis Statistical Modelling and Computational Learning,Visual Object Classes(PASCAL VOC)demonstrate the validity of the proposedmethod.Experimental results show a significant improvement in small object detection accuracy compared to state-of-theart detectors.展开更多
The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of trea...The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.展开更多
As H-and J-aggregation receive more and more attention in the research of organic solar cells(OSCs),especially in small molecular systems,deep understanding of aggregation behavior is needed to guide the design of con...As H-and J-aggregation receive more and more attention in the research of organic solar cells(OSCs),especially in small molecular systems,deep understanding of aggregation behavior is needed to guide the design of conjugated small molecular structure and the fabrication process of OSC device.For this end,this review is written.Here,the review firstly introduced the basic information about H-and J-aggregation of conjugated small molecules in OSCs.Then,the characteristics of H-and J-aggregation and the methods to identify them were summarized.Next,it reviewed the research progress of H-and J-aggregation of conjugated small molecules in OSCs,including the factors influencing H-and J-aggregation in thin film and the effects of H-and J-aggregation on OPV performance.展开更多
BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors ...BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.展开更多
Objective:To examine the socio-environmental factors associated with the assemblage of small mammals and the prevalence of Leptospira pathogen in poor suburban communities of Terengganu,Malaysia.Methods:We trapped sma...Objective:To examine the socio-environmental factors associated with the assemblage of small mammals and the prevalence of Leptospira pathogen in poor suburban communities of Terengganu,Malaysia.Methods:We trapped small mammals from 119 trapping points scattered around three suburban communities of Terengganu using sausage-baited live traps.On the average,we set up five traps for three nights at each sampling point during the trapping period.Kidneys of captured animals were harvested and processed for Leptospira investigation.Additionally,environmental survey was conducted at each trapping point to obtain information about possible variables supporting small mammal assemblage.We used a generalized linear model to evaluate the effect of different socio-environmental variables on small mammals’assemblage.Results:A total of 89 small mammals,specifically,Rattus norvegicus(n=39),Rattus rattus(n=27),Rattus exulans(n=10),Suncus murinus(n=11),and Tupaia glis(n=2)were captured from 1385 trap nights.Fourteen individuals(15.7%)of the captured animals tested positive for Leptospira bacteria using PCR detection.Results of our generalized linear model showed only residences bordering vacant lots as the variable positively associated with small mammal occurrence in the three study sites.Conclusions:Small mammal community,especially the often neglected species,could harbour and potentially contribute towards pathogenic Leptospira maintenance in the study sites.To adequately control small mammals’population and subsequent human zoonoses transmission,it is critical to advocate and promote appropriate infrastructure and suburban services,together with good hygiene practices that can reduce the animals’access to food and harborage.展开更多
In this paper,we consider pseudoharmonic heat flow with small initial horizontal energy and give the existence of pseudoharmonic maps from closed pseudo-Hermitian manifolds into closed Riemannian manifolds.
●AIM:To investigate the long-term changes of corneal densitometry(CD)and its contributing elements after small incision lenticule extraction(SMILE).●METHODS:Totally 31 eyes of 31 patients with mean spherical equival...●AIM:To investigate the long-term changes of corneal densitometry(CD)and its contributing elements after small incision lenticule extraction(SMILE).●METHODS:Totally 31 eyes of 31 patients with mean spherical equivalent of-6.46±1.50 D and mean age 28.23±7.38y were enrolled.Full-scale examinations were conducted on all patients preoperatively and during followup.Visual acuity,manifest refraction,axial length,corneal thickness,corneal higher-order aberrations,and CD were evaluated.●RESULTS:All surgeries were completed successfully without complications or adverse events.Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28.CD value of 0–6 mm zones in central layer was statistically significantly lower 10y postoperatively,compared with preoperative values(0–2 mmΔ=-1.62,2–6 mmΔ=-1.24,P<0.01).There were no correlations between CD values and factors evaluated.●CONCLUSION:SMILE is a safe and efficient procedure for myopia on a long-term basis.CD values get lower 10y postoperatively,whose mechanism is to be further discussed.展开更多
基金supported by the NIH grants,R01 NS111801(to ZGZ)American Heart Association 16SDG29860003(to YZ)。
文摘Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金supported by NIH grants AG079264(to PHR)and AG071560(to APR)。
文摘The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.
基金the National Natural Science Foundation of China,No.82273457Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012180 and No.2023A1515012762+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040and Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.
基金This research was funded by the Natural Science Foundation of Hebei Province(F2021506004).
文摘Transformer-based models have facilitated significant advances in object detection.However,their extensive computational consumption and suboptimal detection of dense small objects curtail their applicability in unmanned aerial vehicle(UAV)imagery.Addressing these limitations,we propose a hybrid transformer-based detector,H-DETR,and enhance it for dense small objects,leading to an accurate and efficient model.Firstly,we introduce a hybrid transformer encoder,which integrates a convolutional neural network-based cross-scale fusion module with the original encoder to handle multi-scale feature sequences more efficiently.Furthermore,we propose two novel strategies to enhance detection performance without incurring additional inference computation.Query filter is designed to cope with the dense clustering inherent in drone-captured images by counteracting similar queries with a training-aware non-maximum suppression.Adversarial denoising learning is a novel enhancement method inspired by adversarial learning,which improves the detection of numerous small targets by counteracting the effects of artificial spatial and semantic noise.Extensive experiments on the VisDrone and UAVDT datasets substantiate the effectiveness of our approach,achieving a significant improvement in accuracy with a reduction in computational complexity.Our method achieves 31.9%and 21.1%AP on the VisDrone and UAVDT datasets,respectively,and has a faster inference speed,making it a competitive model in UAV image object detection.
基金funded by the General Project of Key Research and Develop-ment Plan of Shaanxi Province(No.2022NY-087).
文摘To address the challenges of high complexity,poor real-time performance,and low detection rates for small target vehicles in existing vehicle object detection algorithms,this paper proposes a real-time lightweight architecture based on You Only Look Once(YOLO)v5m.Firstly,a lightweight upsampling operator called Content-Aware Reassembly of Features(CARAFE)is introduced in the feature fusion layer of the network to maximize the extraction of deep-level features for small target vehicles,reducing the missed detection rate and false detection rate.Secondly,a new prediction layer for tiny targets is added,and the feature fusion network is redesigned to enhance the detection capability for small targets.Finally,this paper applies L1 regularization to train the improved network,followed by pruning and fine-tuning operations to remove redundant channels,reducing computational and parameter complexity and enhancing the detection efficiency of the network.Training is conducted on the VisDrone2019-DET dataset.The experimental results show that the proposed algorithmreduces parameters and computation by 63.8% and 65.8%,respectively.The average detection accuracy improves by 5.15%,and the detection speed reaches 47 images per second,satisfying real-time requirements.Compared with existing approaches,including YOLOv5m and classical vehicle detection algorithms,our method achieves higher accuracy and faster speed for real-time detection of small target vehicles in edge computing.
文摘BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.
基金supported by the National Natural Science Foundation of China(Grant Nos.82203539 and 92259102)Provincial Cooperation Project of Science and Technology Department of Sichuan Province(Grant No.2023YFSY0043)the National Key Research and Development Program of China(Grant No.2023YFC3402100).
文摘Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
基金supported by the National Natural Science Foundation of China,Nos.82274611 (to LZ),82104419 (to DM)Capital Science and Technology Leading Talent Training Project,No.Z1 91100006119017 (to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803 (to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006 (to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017 (to DM)Beijing Gold-Bridge Project,No.ZZ20145 (to DM)。
文摘Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
基金supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX)the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。
文摘Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.
文摘Effective small object detection is crucial in various applications including urban intelligent transportation and pedestrian detection.However,small objects are difficult to detect accurately because they contain less information.Many current methods,particularly those based on Feature Pyramid Network(FPN),address this challenge by leveraging multi-scale feature fusion.However,existing FPN-based methods often suffer from inadequate feature fusion due to varying resolutions across different layers,leading to suboptimal small object detection.To address this problem,we propose the Two-layerAttention Feature Pyramid Network(TA-FPN),featuring two key modules:the Two-layer Attention Module(TAM)and the Small Object Detail Enhancement Module(SODEM).TAM uses the attention module to make the network more focused on the semantic information of the object and fuse it to the lower layer,so that each layer contains similar semantic information,to alleviate the problem of small object information being submerged due to semantic gaps between different layers.At the same time,SODEM is introduced to strengthen the local features of the object,suppress background noise,enhance the information details of the small object,and fuse the enhanced features to other feature layers to ensure that each layer is rich in small object information,to improve small object detection accuracy.Our extensive experiments on challenging datasets such as Microsoft Common Objects inContext(MSCOCO)and Pattern Analysis Statistical Modelling and Computational Learning,Visual Object Classes(PASCAL VOC)demonstrate the validity of the proposedmethod.Experimental results show a significant improvement in small object detection accuracy compared to state-of-theart detectors.
文摘The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.
基金financially supported by the National Natural Science Foundation of China(52203024,22225504)the Shandong Provincial Natural Science Foundation(ZR2022QE135)+2 种基金the Youth Innovation Team Project of Shandong Provincial University(2023KJ330)the Qilu University of Technology strong base plan(2023PY001)Guangdong Provincial Key Laboratory of Catalysis(2020B121201002)。
文摘As H-and J-aggregation receive more and more attention in the research of organic solar cells(OSCs),especially in small molecular systems,deep understanding of aggregation behavior is needed to guide the design of conjugated small molecular structure and the fabrication process of OSC device.For this end,this review is written.Here,the review firstly introduced the basic information about H-and J-aggregation of conjugated small molecules in OSCs.Then,the characteristics of H-and J-aggregation and the methods to identify them were summarized.Next,it reviewed the research progress of H-and J-aggregation of conjugated small molecules in OSCs,including the factors influencing H-and J-aggregation in thin film and the effects of H-and J-aggregation on OPV performance.
文摘BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.
文摘Objective:To examine the socio-environmental factors associated with the assemblage of small mammals and the prevalence of Leptospira pathogen in poor suburban communities of Terengganu,Malaysia.Methods:We trapped small mammals from 119 trapping points scattered around three suburban communities of Terengganu using sausage-baited live traps.On the average,we set up five traps for three nights at each sampling point during the trapping period.Kidneys of captured animals were harvested and processed for Leptospira investigation.Additionally,environmental survey was conducted at each trapping point to obtain information about possible variables supporting small mammal assemblage.We used a generalized linear model to evaluate the effect of different socio-environmental variables on small mammals’assemblage.Results:A total of 89 small mammals,specifically,Rattus norvegicus(n=39),Rattus rattus(n=27),Rattus exulans(n=10),Suncus murinus(n=11),and Tupaia glis(n=2)were captured from 1385 trap nights.Fourteen individuals(15.7%)of the captured animals tested positive for Leptospira bacteria using PCR detection.Results of our generalized linear model showed only residences bordering vacant lots as the variable positively associated with small mammal occurrence in the three study sites.Conclusions:Small mammal community,especially the often neglected species,could harbour and potentially contribute towards pathogenic Leptospira maintenance in the study sites.To adequately control small mammals’population and subsequent human zoonoses transmission,it is critical to advocate and promote appropriate infrastructure and suburban services,together with good hygiene practices that can reduce the animals’access to food and harborage.
文摘In this paper,we consider pseudoharmonic heat flow with small initial horizontal energy and give the existence of pseudoharmonic maps from closed pseudo-Hermitian manifolds into closed Riemannian manifolds.
文摘●AIM:To investigate the long-term changes of corneal densitometry(CD)and its contributing elements after small incision lenticule extraction(SMILE).●METHODS:Totally 31 eyes of 31 patients with mean spherical equivalent of-6.46±1.50 D and mean age 28.23±7.38y were enrolled.Full-scale examinations were conducted on all patients preoperatively and during followup.Visual acuity,manifest refraction,axial length,corneal thickness,corneal higher-order aberrations,and CD were evaluated.●RESULTS:All surgeries were completed successfully without complications or adverse events.Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28.CD value of 0–6 mm zones in central layer was statistically significantly lower 10y postoperatively,compared with preoperative values(0–2 mmΔ=-1.62,2–6 mmΔ=-1.24,P<0.01).There were no correlations between CD values and factors evaluated.●CONCLUSION:SMILE is a safe and efficient procedure for myopia on a long-term basis.CD values get lower 10y postoperatively,whose mechanism is to be further discussed.