Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Correlation between the rock mass properties and maximum horizontal stress:A case study of overcoring stress measurements

Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress magnitude.To investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution method.The results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with depth.There is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and messy.Moreover,there is no obvious relationship between the rock quality designation(RQD)and depth.The maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same depth.In addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.

Advancing healthcare through laboratory on a chip technology:Transforming microorganism identification and diagnostics

In a recent case report in the World Journal of Clinical Cases,emphasized the crucial role of rapidly and accurately identifying pathogens to optimize patient treatment outcomes.Laboratory-on-a-chip(LOC)technology has emerged as a transformative tool in health care,offering rapid,sensitive,and specific identification of microorganisms.This editorial provides a comprehensive overview of LOC technology,highlighting its principles,advantages,applications,challenges,and future directions.Success studies from the field have demonstrated the practical benefits of LOC devices in clinical diagnostics,epidemiology,and food safety.Comparative studies have underscored the superiority of LOC technology over traditional methods,showcasing improvements in speed,accuracy,and portability.The future integration of LOC with biosensors,artificial intelligence,and data analytics promises further innovation and expansion.This call to action emphasizes the importance of continued research,investment,and adoption to realize the full potential of LOC technology in improving healthcare outcomes worldwide.

Identification and evaluation of shale oil micromigration and its petroleum geological significance

Taking the Lower Permian Fengcheng Formation shale in Mahu Sag of Junggar Basin,NW China,as an example,core observation,test analysis,geological analysis and numerical simulation were applied to identify the shale oil micro-migration phenomenon.The hydrocarbon micro-migration in shale oil was quantitatively evaluated and verified by a self-created hydrocarbon expulsion potential method,and the petroleum geological significance of shale oil micro-migration evaluation was determined.Results show that significant micro-migration can be recognized between the organic-rich lamina and organic-poor lamina.The organic-rich lamina has strong hydrocarbon generation ability.The heavy components of hydrocarbon preferentially retained by kerogen swelling or adsorption,while the light components of hydrocarbon were migrated and accumulated to the interbedded felsic or carbonate organic-poor laminae as free oil.About 69% of the Fengcheng Formation shale samples in Well MY1 exhibit hydrocarbon charging phenomenon,while 31% of those exhibit hydrocarbon expulsion phenomenon.The reliability of the micro-migration evaluation results was verified by combining the group components based on the geochromatography effect,two-dimension nuclear magnetic resonance analysis,and the geochemical behavior of inorganic manganese elements in the process of hydrocarbon migration.Micro-migration is a bridge connecting the hydrocarbon accumulation elements in shale formations,which reflects the whole process of shale oil generation,expulsion and accumulation,and controls the content and composition of shale oil.The identification and evaluation of shale oil micro-migration will provide new perspectives for dynamically differential enrichment mechanism of shale oil and establishing a“multi-peak model in oil generation”of shale.

Two-Staged Method for Ice Channel Identification Based on Image Segmentation and Corner Point Regression

Identification of the ice channel is the basic technology for developing intelligent ships in ice-covered waters,which is important to ensure the safety and economy of navigation.In the Arctic,merchant ships with low ice class often navigate in channels opened up by icebreakers.Navigation in the ice channel often depends on good maneuverability skills and abundant experience from the captain to a large extent.The ship may get stuck if steered into ice fields off the channel.Under this circumstance,it is very important to study how to identify the boundary lines of ice channels with a reliable method.In this paper,a two-staged ice channel identification method is developed based on image segmentation and corner point regression.The first stage employs the image segmentation method to extract channel regions.In the second stage,an intelligent corner regression network is proposed to extract the channel boundary lines from the channel region.A non-intelligent angle-based filtering and clustering method is proposed and compared with corner point regression network.The training and evaluation of the segmentation method and corner regression network are carried out on the synthetic and real ice channel dataset.The evaluation results show that the accuracy of the method using the corner point regression network in the second stage is achieved as high as 73.33%on the synthetic ice channel dataset and 70.66%on the real ice channel dataset,and the processing speed can reach up to 14.58frames per second.

A real-time intelligent lithology identification method based on a dynamic felling strategy weighted random forest algorithm

Real-time intelligent lithology identification while drilling is vital to realizing downhole closed-loop drilling. The complex and changeable geological environment in the drilling makes lithology identification face many challenges. This paper studies the problems of difficult feature information extraction,low precision of thin-layer identification and limited applicability of the model in intelligent lithologic identification. The author tries to improve the comprehensive performance of the lithology identification model from three aspects: data feature extraction, class balance, and model design. A new real-time intelligent lithology identification model of dynamic felling strategy weighted random forest algorithm(DFW-RF) is proposed. According to the feature selection results, gamma ray and 2 MHz phase resistivity are the logging while drilling(LWD) parameters that significantly influence lithology identification. The comprehensive performance of the DFW-RF lithology identification model has been verified in the application of 3 wells in different areas. By comparing the prediction results of five typical lithology identification algorithms, the DFW-RF model has a higher lithology identification accuracy rate and F1 score. This model improves the identification accuracy of thin-layer lithology and is effective and feasible in different geological environments. The DFW-RF model plays a truly efficient role in the realtime intelligent identification of lithologic information in closed-loop drilling and has greater applicability, which is worthy of being widely used in logging interpretation.

A Novel On-Site-Real-Time Method for Identifying Characteristic Parameters Using Ultrasonic Echo Groups and Neural Network

On-site and real-time non-destructive measurement of elastic constants for materials of a component in a in-service structure is a challenge due to structural complexities,such as ambiguous boundary,variable thickness,nonuniform material properties.This work develops for the first time a method that uses ultrasound echo groups and artificial neural network(ANN)for reliable on-site real-time identification of material parameters.The use of echo groups allows the use of lower frequencies,and hence more accommodative to structural complexity.To train the ANNs,a numerical model is established that is capable of computing the waveform of ultrasonic echo groups for any given set of material properties of a given structure.The waveform of an ultrasonic echo groups at an interest location on the surface the structure with material parameters varying in a predefined range are then computed using the numerical model.This results in a set of dataset for training the ANN model.Once the ANN is trained,the material parameters can be identified simultaneously using the actual measured echo waveform as input to the ANN.Intensive tests have been conducted both numerically and experimentally to evaluate the effectiveness and accuracy of the currently proposed method.The results show that the maximum identification error of numerical example is less than 2%,and the maximum identification error of experimental test is less than 7%.Compared with currently prevailing methods and equipment,the proposefy the density and thickness,in addition to the elastic constants.Moreover,the reliability and accuracy of inverse prediction is significantly improved.Thus,it has broad applications and enables real-time field measurements,which has not been fulfilled by any other available methods or equipment.

Flexible bidirectional pulse charging regulation achieving long-life lithium-ion batteries

Typical application scenarios,such as vehicle to grid(V2G)and frequency regulation,have imposed significant long-life demands on lithium-ion batteries.Herein,we propose an advanced battery life-extension method employing bidirectional pulse charging(BPC)strategy.Unlike traditional constant current charging methods,BPC strategy not only achieves comparable charging speeds but also facilitates V2G frequency regulation simultaneously.It significantly enhances battery cycle ampere-hour throughput and demonstrates remarkable life extension capabilities.For this interesting conclusion,adopting model identification and postmortem characterization to reveal the life regulation mechanism of BPC:it mitigates battery capacity loss attributed to loss of lithium-ion inventory(LLI)in graphite anodes by intermittently regulating the overall battery voltage and anode potential using a negative charging current.Then,from the perspective of internal side reaction,the life extension mechanism is further revealed as inhibition of solid electrolyte interphase(SEI)and lithium dendrite growth by regulating voltage with a bidirectional pulse current,and a semi-empirical life degradation model combining SEI and lithium dendrite growth is developed for BPC scenarios health management,the model parameters are identified by genetic algorithm with the life simulation exhibiting an accuracy exceeding 99%.This finding indicates that under typical rate conditions,adaptable BPC strategies can extend the service life of LFP battery by approximately 123%.Consequently,the developed advanced BPC strategy offers innovative perspectives and insights for the development of long-life battery applications in the future.

Dynamic Hand Gesture-Based Person Identification Using Leap Motion and Machine Learning Approaches

Person identification is one of the most vital tasks for network security. People are more concerned about theirsecurity due to traditional passwords becoming weaker or leaking in various attacks. In recent decades, fingerprintsand faces have been widely used for person identification, which has the risk of information leakage as a resultof reproducing fingers or faces by taking a snapshot. Recently, people have focused on creating an identifiablepattern, which will not be reproducible falsely by capturing psychological and behavioral information of a personusing vision and sensor-based techniques. In existing studies, most of the researchers used very complex patternsin this direction, which need special training and attention to remember the patterns and failed to capturethe psychological and behavioral information of a person properly. To overcome these problems, this researchdevised a novel dynamic hand gesture-based person identification system using a Leap Motion sensor. Thisstudy developed two hand gesture-based pattern datasets for performing the experiments, which contained morethan 500 samples, collected from 25 subjects. Various static and dynamic features were extracted from the handgeometry. Randomforest was used to measure feature importance using the Gini Index. Finally, the support vectormachinewas implemented for person identification and evaluate its performance using identification accuracy. Theexperimental results showed that the proposed system produced an identification accuracy of 99.8% for arbitraryhand gesture-based patterns and 99.6% for the same dynamic hand gesture-based patterns. This result indicatedthat the proposed system can be used for person identification in the field of security.

Applying an Improved Dung Beetle Optimizer Algorithm to Network Traffic Identification

Network traffic identification is critical for maintaining network security and further meeting various demands of network applications.However,network traffic data typically possesses high dimensionality and complexity,leading to practical problems in traffic identification data analytics.Since the original Dung Beetle Optimizer(DBO)algorithm,Grey Wolf Optimization(GWO)algorithm,Whale Optimization Algorithm(WOA),and Particle Swarm Optimization(PSO)algorithm have the shortcomings of slow convergence and easily fall into the local optimal solution,an Improved Dung Beetle Optimizer(IDBO)algorithm is proposed for network traffic identification.Firstly,the Sobol sequence is utilized to initialize the dung beetle population,laying the foundation for finding the global optimal solution.Next,an integration of levy flight and golden sine strategy is suggested to give dung beetles a greater probability of exploring unvisited areas,escaping from the local optimal solution,and converging more effectively towards a global optimal solution.Finally,an adaptive weight factor is utilized to enhance the search capabilities of the original DBO algorithm and accelerate convergence.With the improvements above,the proposed IDBO algorithm is then applied to traffic identification data analytics and feature selection,as so to find the optimal subset for K-Nearest Neighbor(KNN)classification.The simulation experiments use the CICIDS2017 dataset to verify the effectiveness of the proposed IDBO algorithm and compare it with the original DBO,GWO,WOA,and PSO algorithms.The experimental results show that,compared with other algorithms,the accuracy and recall are improved by 1.53%and 0.88%in binary classification,and the Distributed Denial of Service(DDoS)class identification is the most effective in multi-classification,with an improvement of 5.80%and 0.33%for accuracy and recall,respectively.Therefore,the proposed IDBO algorithm is effective in increasing the efficiency of traffic identification and solving the problem of the original DBO algorithm that converges slowly and falls into the local optimal solution when dealing with high-dimensional data analytics and feature selection for network traffic identification.

Association between childhood obesity and gut microbiota:16S rRNA gene sequencing-based cohort study

BACKGROUND This study aimed to identify characteristic gut genera in obese and normal-weight children(8-12 years old)using 16S rDNA sequencing.The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity.Thirty normal-weight and thirty age-and sex-matched obese children were included.Questionnaires and body measurements were collected,and fecal samples underwent 16S rDNA sequencing.Significant differences in body mass index(BMI)and body-fat percentage were observed between the groups.Analysis of gut microbiota diversity revealed lowerα-diversity in obese children.Differences in gut microbiota composition were found between the two groups.Prevotella and Firmicutes were more abundant in the obese group,while Bacteroides and Sanguibacteroides were more prevalent in the control group.AIM To identify the characteristic gut genera in obese and normal-weight children(8-12-year-old)using 16S rDNA sequencing,and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity.METHODS Thirty each normal-weight,1:1 matched for age and sex,and obese children,with an obese status from 2020 to 2022,were included in the control and obese groups,respectively.Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children.Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis.RESULTS Significant differences in BMI and body-fat percentage were observed between the two groups.The Ace and Chao1 indices were significantly lower in the obese group than those in the control group,whereas differences were not significant in the Shannon and Simpson indices.Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children(P<0.01),suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups.Prevotella,Firmicutes,Bacteroides,and Sanguibacteroides were more abundant in the obese and control groups,respectively.Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children.CONCLUSION Obese children exhibited lowerα-diversity in their gut microbiota than did the normal-weight children.Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Eikenella corrodens isolated from pleural effusion:A case report

BACKGROUND The bacterium Eikenella,classified as a gram-negative member of the phylum Proteobacteria,is distinguished by its rarity,corrosive nature,facultative anaerobic properties,and conditional pathogenicity.It represents the sole species within its genus-Eikenella corrodens(E.corrodens)-and can be found colonizing both human and animal oral and nasopharyngeal regions.Additionally,it occasionally inhabits the gastrointestinal or urogenital tracts.However,its slow growth rate can be attributed to its high nutritional requirements.However,there is an uneven distribution of construction and diagnostic capacity in China which poses undeniable challenges for the clinical examination and analysis of this case,especially in the basic hospitals.CASE SUMMARY Here we presented a case of empyema associated with E.corrodens infection in a 67-year-old male patient without any previous history of infectious diseases in our primary hospital in Dongguan district of China.The patient was admitted due to recurrent worsening cough,sputum production,and dyspnea for 3 d,which had persisted for over 20 years.Moreover,the patient experienced a onehour episode of unconsciousness.Upon admission,immediate comprehensive examinations were conducted on the patient which subsequently led to his admission to the intensive care unit.Meanwhile,the patient presented with drowsiness and profuse sweating along with bilateral conjunctival edema observed during initiation of non-invasive ventilation,suggesting empyema.A significant amount of coffee-colored malodorous pleural fluid was drained during the procedure above and sent to the laboratory department for inspection.Finally,laboratory culture results confirmed the presence of E.corrodens infection in the pleural fluid sample.The patient received antimicrobial therapy until died on day 22 in the hospital.CONCLUSION In this report,we presented a case of empyema associated with E.corrodens infection.Multiple courses of morphological examination,viable culture analysis,and biochemical identification revealed its difficulties in detecting distinctive characteristics,as well as a detection model worth promoting.It’s just that there were still certain deficiencies in terms of morphological assessment,biochemical identification,and drug susceptibility testing.

Pollution source identification methods and remediation technologies of groundwater: A review

Groundwater is an important source of drinking water.Groundwater pollution severely endangers drinking water safety and sustainable social development.In the case of groundwater pollution,the top priority is to identify pollution sources,and accurate information on pollution sources is the premise of efficient remediation.Then,an appropriate pollution remediation scheme should be developed according to information on pollution sources,site conditions,and economic costs.The methods for identifying pollution sources mainly include geophysical exploration,geochemistry,isotopic tracing,and numerical modeling.Among these identification methods,only the numerical modeling can recognize various information on pollution sources,while other methods can only identify a certain aspect of pollution sources.The remediation technologies of groundwater can be divided into in-situ and ex-situ remediation technologies according to the remediation location.The in-situ remediation technologies enjoy low costs and a wide remediation range,but their remediation performance is prone to be affected by environmental conditions and cause secondary pollution.The ex-situ remediation technologies boast high remediation efficiency,high processing capacity,and high treatment concentration but suffer high costs.Different methods for pollution source identification and remediation technologies are applicable to different conditions.To achieve the expected identification and remediation results,it is feasible to combine several methods and technologies according to the actual hydrogeological conditions of contaminated sites and the nature of pollutants.Additionally,detailed knowledge about the hydrogeological conditions and stratigraphic structure of the contaminated site is the basis of all work regardless of the adopted identification methods or remediation technologies.

Concise extraction and characterization of the pore-throat network in unconventional hydrocarbon reservoirs: A new perspective

In this study,a new image-based method for the extraction and characterization of pore-throat network for unconventional hydrocarbon storage and exploitation is proposed.“Pore-throat solidity”,which is analogous to particle solidity,and a new method for automatic identification of pores and throats in tight sandstone oil reservoirs are introduced.Additionally,the“pore-throat combination”and“pure pore”are defined and distinguished by drawing the cumulative probability curve of the pore-throat solidity and by selecting an appropriate cutoff point.When the discrete grid set is recognized as a pore-throat combination,Legendre ellipse fitting and minimum Feret diameter are used.When the pore and throat grid sets are identified as pure pores,the pore diameter can be directly calculated.Using the new method,the analytical results for the physical parameters and pore radius agree well with most prior studies.The results comparing the maximum ball and the new model could also prove the accuracy of the latter's in micro and nano scales.The new model provides a more practical theoretical basis and a new calculation method for the rapid and accurate evaluation of the complex processes of oil migration.

Integrative analysis of transcriptomic profile reveals potential roles of miRNAs in regulating development of Marsupenaeus japonicas

Regulation of microRNAs(miRNAs)on various biological processes has been a surprising and exciting field.Identification of miRNAs is the first step to comprehensively understand their functions.However,attempts on global identification and functional verification of miRNAs are very limited in penaeid shrimp Marsupenaeus japonicus,an economically important aquatic species.By performing an integrated analysis of transcriptomic profile from gastrula embryos of M.japonicus,21conserved miRNAs in M.japonicas(mja-miRNAs),belonging to 19 miRNA families,were identified and characterized.Of the 21 mja-miRNAs,15 miRNAs were successfully verified to be predominantly expressed in gastrula stage,where they displayed dynamic expression patterns compared with those in naupliuin stage.Based on perfect or near-perfect match to target region,120 target genes were predicted at transcriptome-wide level.Noteworthy,gene ontology(GO)classification and metabolic pathway annotation revealed eight targets that were actively involved in developmental processes.Of the predicted miRNA-mRNA pairs,six targets were then randomly selected and experimentally validated by dual luciferase reporter assay,where three pairs were proved with potential targeting activity.Overall,to search for conserved miRNAs potentially involved in early development of M.japonicus,we combined in silico and experimental methods,which can be applied in other organisms as well.Our data implied important roles of miRNAs in the early embryonic development and also suggested the presence of complex miRNA-mRNA functional networks in M.japonicus.

Genes controlling grain chalkiness in rice

With rising living standards,there is an increasing demand for high-quality rice.Rice quality is mainly defined by milling quality,appearance quality,cooking and eating quality,and nutrition quality.Among them,chalkiness is a key trait for appearance quality,which adversely affects cooking and eating quality,head rice yield,and commercial value.Therefore,chalkiness is undesirable,and reducing chalkiness is a major goal in rice quality improvement.However,chalkiness is a complex trait jointly influenced by genetic and environmental factors,making its genetic study and precision improvement a huge challenge.With the rapid development of molecular techniques,much knowledge has been gained about the genes and molecular networks involved in chalkiness formation.The present review describes the major environmental factors affecting chalkiness and summarizes the quantitative trait loci(QTL)associated with chalkiness.More than 150 genes related to chalkiness formation have been reported.The functions of the genes regulating chalkiness,primarily those involved in starch synthesis,storage protein synthesis,transcription regulation,organelle development,grain shape regulation,and hightemperature response,are described.Finally,we identify the challenges associated with genetic improvement of chalkiness and suggest potential strategies.Thus,the review offers insight into the molecular dynamics of chalkiness and provides a strong basis for the future breeding of high-quality rice varieties.

Nondestructive technique for identifying nuclides using neutron resonance transmission analysis at CSNS Back-n

Nondestructive and noninvasive neutron assays are essential applications of neutron techniques.Neutron resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental composition of an object.The back-streaming neutron line(Back-n)is a newly built time-of-flight facility at the China Spallation Neutron Source(CSNS)that provides neutrons in the eV to 300 MeV range.A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test experiments.The results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at Back-n.This study reveals its potential future applications.

Dynamics Modeling and Parameter Identification for a Coupled-Drive Dual-Arm Nursing Robot

A dual-arm nursing robot can gently lift patients and transfer them between a bed and a wheelchair.With its lightweight design,high load-bearing capacity,and smooth surface,the coupled-drive joint is particularly well suited for these robots.However,the coupled nature of the joint disrupts the direct linear relationship between the input and output torques,posing challenges for dynamic modeling and practical applications.This study investigated the transmission mechanism of this joint and employed the Lagrangian method to construct a dynamic model of its internal dynamics.Building on this foundation,the Newton-Euler method was used to develop a dynamic model for the entire robotic arm.A continuously differentiable friction model was incorporated to reduce the vibrations caused by speed transitions to zero.An experimental method was designed to compensate for gravity,inertia,and modeling errors to identify the parameters of the friction model.This method establishes a mapping relationship between the friction force and motor current.In addition,a Fourier series-based excitation trajectory was developed to facilitate the identification of the dynamic model parameters of the robotic arm.Trajectory tracking experiments were conducted during the experimental validation phase,demonstrating the high accuracy of the dynamic model and the parameter identification method for the robotic arm.This study presents a dynamic modeling and parameter identification method for coupled-drive joint robotic arms,thereby establishing a foundation for motion control in humanoid nursing robots.

Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.

Digital Image Steganographer Identification:A Comprehensive Survey

The rapid development of the internet and digital media has provided convenience while also posing a potential risk of steganography abuse.Identifying steganographer is essential in tracing secret information origins and preventing illicit covert communication online.Accurately discerning a steganographer from many normal users is challenging due to various factors,such as the complexity in obtaining the steganography algorithm,extracting highly separability features,and modeling the cover data.After extensive exploration,several methods have been proposed for steganographer identification.This paper presents a survey of existing studies.Firstly,we provide a concise introduction to the research background and outline the issue of steganographer identification.Secondly,we present fundamental concepts and techniques that establish a general framework for identifying steganographers.Within this framework,state-of-the-art methods are summarized from five key aspects:data acquisition,feature extraction,feature optimization,identification paradigm,and performance evaluation.Furthermore,theoretical and experimental analyses examine the advantages and limitations of these existing methods.Finally,the survey highlights outstanding issues in image steganographer identification that deserve further research.