Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has ev...Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has evolved as a potential therapeutic option for treating Alzheimer’s disease,owing to its rapid advancement over the recent decade.Small interfering ribonucleic acid has recently garnered considerable attention in gene therapy owing to its ability to down-regulate genes with high sequence specificity and an almost limitless number of therapeutic targets,including those that were once considered undruggable.However,lackluster cellular uptake and the destabilization of small interfering ribonucleic acid in its biological environment restrict its therapeutic application,necessitating the development of a vector that can safeguard the genetic material from early destruction within the bloodstream while effectively delivering therapeutic genes across the bloodbrain barrier.Nanotechnology has emerged as a possible solution,and several delivery systems utilizing nanoparticles have been shown to bypass key challenges regarding small interfering ribonucleic acid delivery.By reducing the enzymatic breakdown of genetic components,nanomaterials as gene carriers have considerably enhanced the efficiency of gene therapy.Liposomes,polymeric nanoparticles,magnetic nanoparticles,dendrimers,and micelles are examples of nanocarriers that have been designed,and each has its own set of features.Furthermore,recent advances in the specific delivery of neurotrophic compounds via gene therapy have provided promising results in relation to augmenting cognitive abilities.In this paper,we highlight the use of different nanocarriers in targeted gene delivery and small interfering ribonucleic acid-mediated gene silencing as a potential platform for treating Alzheimer’s disease.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
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
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
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
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
The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool...The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.展开更多
BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diag...BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its treatment.Therefore,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and prognosis.AIM To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine.METHODS The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the Air Force Medical Center,Chinese People’s Liberation Army.Then descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and prognosis.RESULTS Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular cancer.The median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases.The small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstruction(4,36.4%).In addition,2 patients had no obvious symptoms at the diagnosis of small intestinal metastases,and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery.A total of 3 patients did not receive subsequent treatment due to advanced conditions.CONCLUSION Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment.Clinically,patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease,and their prognosis may be improved through active surgery combined with standard targeted therapy.展开更多
Accurately identifying small objects in high-resolution aerial images presents a complex and crucial task in thefield of small object detection on unmanned aerial vehicles(UAVs).This task is challenging due to variati...Accurately identifying small objects in high-resolution aerial images presents a complex and crucial task in thefield of small object detection on unmanned aerial vehicles(UAVs).This task is challenging due to variations inUAV flight altitude,differences in object scales,as well as factors like flight speed and motion blur.To enhancethe detection efficacy of small targets in drone aerial imagery,we propose an enhanced You Only Look Onceversion 7(YOLOv7)algorithm based on multi-scale spatial context.We build the MSC-YOLO model,whichincorporates an additional prediction head,denoted as P2,to improve adaptability for small objects.We replaceconventional downsampling with a Spatial-to-Depth Convolutional Combination(CSPDC)module to mitigatethe loss of intricate feature details related to small objects.Furthermore,we propose a Spatial Context Pyramidwith Multi-Scale Attention(SCPMA)module,which captures spatial and channel-dependent features of smalltargets acrossmultiple scales.This module enhances the perception of spatial contextual features and the utilizationof multiscale feature information.On the Visdrone2023 and UAVDT datasets,MSC-YOLO achieves remarkableresults,outperforming the baseline method YOLOv7 by 3.0%in terms ofmean average precision(mAP).The MSCYOLOalgorithm proposed in this paper has demonstrated satisfactory performance in detecting small targets inUAV aerial photography,providing strong support for practical applications.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
Small mountainous rivers are characterized by large instantaneous fluxes and susceptible to extreme weather events,which can rapidly transport materials into the sea and have a significant impact on the ecological env...Small mountainous rivers are characterized by large instantaneous fluxes and susceptible to extreme weather events,which can rapidly transport materials into the sea and have a significant impact on the ecological environment of estuaries and bays.In order to investigate the seasonal characteristics of nutrients in small mountainous rivers in the subtropical monsoon region and the output pattern to the sea during heavy precipitation,surveys on the mountainous rivers were carried out in Baixi watershed in August 2020(wet season),March 2021(dry season)and June 2021(Meiyu period).The results showed that the dissolved inorganic nitrogen(DIN)of the rivers has an average concentration of 752μg L^(−1)in the wet season and 1472μg L^(−1)in the dry season.The concentrations of dissolved inorganic phosphorus(DIP)in wet season and dry season were 63μg L^(−1)and 51μg L^(−1),respectively.Influenced by the changes of land use in sub-watersheds,DIN concentrations in the mainstream increased from 701μg L^(−1)in the upper reaches to 1284μg L^(−1)in the middle reaches.Two rainstorms during the Meiyu period in the watershed caused the pulse runoff in the river.The maximum daily runoff reached 70 times that before rains.The maximum daily fluxes of DIN and DIP were 109 and 247 times that before rains,respectively.In view that the watershed experienced several rainstorms in the wet season,the river,with pulse runoff,carries a large amount of nutrients into the sea in a short time,which will have a significant impact on the environment of Sanmen bay and its adjacent sea.展开更多
Insulator defect detection plays a vital role in maintaining the secure operation of power systems.To address the issues of the difficulty of detecting small objects and missing objects due to the small scale,variable...Insulator defect detection plays a vital role in maintaining the secure operation of power systems.To address the issues of the difficulty of detecting small objects and missing objects due to the small scale,variable scale,and fuzzy edge morphology of insulator defects,we construct an insulator dataset with 1600 samples containing flashovers and breakages.Then a simple and effective surface defect detection method of power line insulators for difficult small objects is proposed.Firstly,a high-resolution featuremap is introduced and a small object prediction layer is added so that the model can detect tiny objects.Secondly,a simplified adaptive spatial feature fusion(SASFF)module is introduced to perform cross-scale spatial fusion to improve adaptability to variable multi-scale features.Finally,we propose an enhanced deformable attention mechanism(EDAM)module.By integrating a gating activation function,the model is further inspired to learn a small number of critical sampling points near reference points.And the module can improve the perception of object morphology.The experimental results indicate that concerning the dataset of flashover and breakage defects,this method improves the performance of YOLOv5,YOLOv7,and YOLOv8.In practical application,it can simply and effectively improve the precision of power line insulator defect detection and reduce missing detection for difficult small objects.展开更多
基金supported by the Intramural Research Program National Institute on Aginq,NIH。
文摘Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has evolved as a potential therapeutic option for treating Alzheimer’s disease,owing to its rapid advancement over the recent decade.Small interfering ribonucleic acid has recently garnered considerable attention in gene therapy owing to its ability to down-regulate genes with high sequence specificity and an almost limitless number of therapeutic targets,including those that were once considered undruggable.However,lackluster cellular uptake and the destabilization of small interfering ribonucleic acid in its biological environment restrict its therapeutic application,necessitating the development of a vector that can safeguard the genetic material from early destruction within the bloodstream while effectively delivering therapeutic genes across the bloodbrain barrier.Nanotechnology has emerged as a possible solution,and several delivery systems utilizing nanoparticles have been shown to bypass key challenges regarding small interfering ribonucleic acid delivery.By reducing the enzymatic breakdown of genetic components,nanomaterials as gene carriers have considerably enhanced the efficiency of gene therapy.Liposomes,polymeric nanoparticles,magnetic nanoparticles,dendrimers,and micelles are examples of nanocarriers that have been designed,and each has its own set of features.Furthermore,recent advances in the specific delivery of neurotrophic compounds via gene therapy have provided promising results in relation to augmenting cognitive abilities.In this paper,we highlight the use of different nanocarriers in targeted gene delivery and small interfering ribonucleic acid-mediated gene silencing as a potential platform for treating Alzheimer’s disease.
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.
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.
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.
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.
文摘The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.
基金Supported by Outstanding Young Talents Program of Air Force Medical Center,People’s Liberation Army,No.22BJQN004Clinical Program of Air Force Medical University,No.Xiaoke2022-07.
文摘BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its treatment.Therefore,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and prognosis.AIM To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine.METHODS The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the Air Force Medical Center,Chinese People’s Liberation Army.Then descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and prognosis.RESULTS Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular cancer.The median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases.The small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstruction(4,36.4%).In addition,2 patients had no obvious symptoms at the diagnosis of small intestinal metastases,and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery.A total of 3 patients did not receive subsequent treatment due to advanced conditions.CONCLUSION Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment.Clinically,patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease,and their prognosis may be improved through active surgery combined with standard targeted therapy.
基金the Key Research and Development Program of Hainan Province(Grant Nos.ZDYF2023GXJS163,ZDYF2024GXJS014)National Natural Science Foundation of China(NSFC)(Grant Nos.62162022,62162024)+2 种基金the Major Science and Technology Project of Hainan Province(Grant No.ZDKJ2020012)Hainan Provincial Natural Science Foundation of China(Grant No.620MS021)Youth Foundation Project of Hainan Natural Science Foundation(621QN211).
文摘Accurately identifying small objects in high-resolution aerial images presents a complex and crucial task in thefield of small object detection on unmanned aerial vehicles(UAVs).This task is challenging due to variations inUAV flight altitude,differences in object scales,as well as factors like flight speed and motion blur.To enhancethe detection efficacy of small targets in drone aerial imagery,we propose an enhanced You Only Look Onceversion 7(YOLOv7)algorithm based on multi-scale spatial context.We build the MSC-YOLO model,whichincorporates an additional prediction head,denoted as P2,to improve adaptability for small objects.We replaceconventional downsampling with a Spatial-to-Depth Convolutional Combination(CSPDC)module to mitigatethe loss of intricate feature details related to small objects.Furthermore,we propose a Spatial Context Pyramidwith Multi-Scale Attention(SCPMA)module,which captures spatial and channel-dependent features of smalltargets acrossmultiple scales.This module enhances the perception of spatial contextual features and the utilizationof multiscale feature information.On the Visdrone2023 and UAVDT datasets,MSC-YOLO achieves remarkableresults,outperforming the baseline method YOLOv7 by 3.0%in terms ofmean average precision(mAP).The MSCYOLOalgorithm proposed in this paper has demonstrated satisfactory performance in detecting small targets inUAV aerial photography,providing strong support for practical applications.
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.
基金financially supported by the Postdoctoral Foundation of Qingdao(Pb Isotopes of Oujiang River to Quantitatively Identify Sediment Provenance in Oujiang Estuary and Adjacent Area)the China Geological Survey Project(No.DD20190276)the Fund of Ministry of Science and Technology(Nos.2013FY112200 and 2019YFE0127200).
文摘Small mountainous rivers are characterized by large instantaneous fluxes and susceptible to extreme weather events,which can rapidly transport materials into the sea and have a significant impact on the ecological environment of estuaries and bays.In order to investigate the seasonal characteristics of nutrients in small mountainous rivers in the subtropical monsoon region and the output pattern to the sea during heavy precipitation,surveys on the mountainous rivers were carried out in Baixi watershed in August 2020(wet season),March 2021(dry season)and June 2021(Meiyu period).The results showed that the dissolved inorganic nitrogen(DIN)of the rivers has an average concentration of 752μg L^(−1)in the wet season and 1472μg L^(−1)in the dry season.The concentrations of dissolved inorganic phosphorus(DIP)in wet season and dry season were 63μg L^(−1)and 51μg L^(−1),respectively.Influenced by the changes of land use in sub-watersheds,DIN concentrations in the mainstream increased from 701μg L^(−1)in the upper reaches to 1284μg L^(−1)in the middle reaches.Two rainstorms during the Meiyu period in the watershed caused the pulse runoff in the river.The maximum daily runoff reached 70 times that before rains.The maximum daily fluxes of DIN and DIP were 109 and 247 times that before rains,respectively.In view that the watershed experienced several rainstorms in the wet season,the river,with pulse runoff,carries a large amount of nutrients into the sea in a short time,which will have a significant impact on the environment of Sanmen bay and its adjacent sea.
基金State Grid Jiangsu Electric Power Co.,Ltd.of the Science and Technology Project(Grant No.J2022004).
文摘Insulator defect detection plays a vital role in maintaining the secure operation of power systems.To address the issues of the difficulty of detecting small objects and missing objects due to the small scale,variable scale,and fuzzy edge morphology of insulator defects,we construct an insulator dataset with 1600 samples containing flashovers and breakages.Then a simple and effective surface defect detection method of power line insulators for difficult small objects is proposed.Firstly,a high-resolution featuremap is introduced and a small object prediction layer is added so that the model can detect tiny objects.Secondly,a simplified adaptive spatial feature fusion(SASFF)module is introduced to perform cross-scale spatial fusion to improve adaptability to variable multi-scale features.Finally,we propose an enhanced deformable attention mechanism(EDAM)module.By integrating a gating activation function,the model is further inspired to learn a small number of critical sampling points near reference points.And the module can improve the perception of object morphology.The experimental results indicate that concerning the dataset of flashover and breakage defects,this method improves the performance of YOLOv5,YOLOv7,and YOLOv8.In practical application,it can simply and effectively improve the precision of power line insulator defect detection and reduce missing detection for difficult small objects.