Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxid...Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.展开更多
African swine fever(ASF),a fatal disease outbroken in China in August 2018,has widely attracted social concern especially in the information era.The occurrence of ASF led to an imbalance between supply and demand in p...African swine fever(ASF),a fatal disease outbroken in China in August 2018,has widely attracted social concern especially in the information era.The occurrence of ASF led to an imbalance between supply and demand in pork and other meat markets.As a result,meat prices fluctuated greatly during the past year in 2019.To measure ASF quantitatively,the internet public concern index about ASF was created using web crawler methods.The relationships between ASF and meat prices were analyzed based on time-varying parameter vector auto-regressive(TVP-VAR)model.The results showed that there were some differences in the impact size,direction and duration of ASF on the prices of pork,chicken,beef and mutton,and the characteristics of time variability and heterogeneity were obvious.At the same time,the impact of ASF on meat prices is not consistent with the trend and degree of ASF.The impulse intensity is strongly correlated with the strength and duration of ASF,and it is generally weak in the early stage and much stronger in the middle and late periods.The results indicate that macro regulations,monitoring and early-warning system,standardizing production and circulation,and the public opinion monitoring and guidance about ASF should be given more attention in future to stabilize the market expectations and to promote a smooth functioning of the livestock markets.展开更多
Objective: To establish a swine model of orthotopic liver transplantation (OLT) which has high standardization, superior reproducibility and stability. Methods: The rate of success, reproducibility and stability were ...Objective: To establish a swine model of orthotopic liver transplantation (OLT) which has high standardization, superior reproducibility and stability. Methods: The rate of success, reproducibility and stability were investigated on the modification of OLTs in closed miniature swine with series of improvements. Results: 20 OLTs were performed on the basis of improvements in experimental animals, surgical procedures and operative monitorings. The mean operation time and anhepatic phase was (181±25.8) and (28.4±3.2) min respectively, which were significantly shorter than those of the previous reports. Liver function of the animals recovered shortly after operation. One-week survival rate was 90%, and 15 animals survived more than 1 month. The incidence of vascular and biliary complications was lower in animals with long-term survival. Conclusion: The improved animal model of OLTs in swine is easy to operate with high standardization and rate of success, superior reproducibility and stability. It is an ideal model for series studies related to liver transplantation in big animals.展开更多
BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving...BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.展开更多
Objective To establish the mitral regurgitation swine model and study the change of hydrogen sulfide(H2S)system in chronic heart failure model.Methods Miniature pigs were randomly divided into two groups,the control g...Objective To establish the mitral regurgitation swine model and study the change of hydrogen sulfide(H2S)system in chronic heart failure model.Methods Miniature pigs were randomly divided into two groups,the control group(n=6)and mitral regurgitation group(n=6).Chronic heart failure models were established by pulling mitral chordal through a small incision extracorporeal.展开更多
Reproducibility of clinical output is important when investigating therapeutic efficacy in pre-clinical animal studies.Due to its physiological relevance,a swine myocardial infarction(MI)model has been widely used to ...Reproducibility of clinical output is important when investigating therapeutic efficacy in pre-clinical animal studies.Due to its physiological relevance,a swine myocardial infarction(MI)model has been widely used to evaluate the effectiveness of stem cells or tissue-engineered constructs for ischemic heart diseases.Several methods are used to induce MI in the swine model.However,it is difficult,using these approaches,to obtain a similar level of functional outcomes from a group of animals due to interpersonal variation,leading to increased experimental cost.Hence,in order to minimize human intervention,we developed an approach to use a customized occluder that has dimensional similarities with that of the coronary artery of animals in the case of the swine model.We carried out angiography to measure the diameter of the middle left anterior descending artery of each individual animal to fabricate the customized occluder using a 3D-printing system.The fabricated occluder contained a central hole smaller than that of the targeted middle left anterior descending artery to mimic an atherosclerotic coronary artery that has an approximately 20%blocked condition.Interestingly,the 3D-printed occluder can provide continuous blood flow through the central pore,indicating a high survival rate(88%)of up to 28 days post-operation.This method showed the possibility of creating consistent myocardial infarction induction as compared to the conventional representative closed-chest method(50%survival rate),thus highlighting how our method can have a profound effect on accelerating reliable experiments for developing new therapeutic approaches to ischemic heart diseases.展开更多
BACKGROUND: In localized brain proton magnetic resonance spectroscopy (^1H-MRS), metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which ...BACKGROUND: In localized brain proton magnetic resonance spectroscopy (^1H-MRS), metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which is assumed to be stable in normal, as well as many pathological, states. However, in vivo creatine levels do not remain constant. Therefore, absolute metabolite measurements, which provide the precise concentrations of certain chemical compounds, are superior to metabolite ratios for determining pathological and evolutional changes. OBJECTIVE: To investigate the feasibility of quantification analysis of brain metabolite changes caused by central analgesics nasal spray using the ^1H-MRS and linear combination model (LCModel) methods. DESIGN, TIME AND SETTING: This neuroimaging, observational, animal study was performed at the Laboratory of the Department of Medical Imaging, Second Affiliated Hospital, Medical College, Shantou University, China from July to December 2007. MATERIALS: Butorphanol tartrate nasal spray, as a mixed agonist-antagonist opioid analgesic, was purchased from Shanghai Hengrui Pharmacy, China. A General Electric Signa 1.5T System (General Electric Medical Systems, Milwaukee, WI, USA) and LCModel software (Stephen Provencher, Oakville, Ontario, Canada) were used in this study. METHODS: MRS images were acquired in ten healthy swine aged 2 weeks using single-voxel point-resolved spectroscopic sequence. A region of interest (2 cm × 2 cm × 2 cm) was placed in the image centers of maximum brain parenchyma. Repeated MRS scanning was performed 15-20 minutes after intranasal administration of 1 mg of butorphanol tartrate. Three settings of repetition time/echo time were selected before and after nasal spray administration 3 000 ms/30 ms,1 500 ms/30 ms, and 3 000 ms/50 ms. Metabolite concentrations were estimated by LCModel software. MAIN OUTCOME MEASURES: ^1H-MRS spectra was obtained using various repetition time/echo time settings. Concentrations of glutamate compounds (glutamate + glutamine), N-acetyl aspartate, and choline were detected in swine brain prior to and following nasal spray treatment. RESULTS: The glutamate compounds curve was consistent with original spectra, when a repetition time/echo time of 3 000 ms/30 ms was adopted. Concentrations of glutamate compounds, N-acetyl aspartate, and choline decreased following administration. The most significant reduction was observed in glutamate compound concentrations from (9.28 ± 0.54) mmol/kg to (7.28 ± 0.54) mmol/kg (P 〈 0.05). CONCLUSION: ^1H-MRS and LCModel software were effectively utilized to quantitatively analyze and measure brain metabolites. Glutamate compounds might be an important neurotransmitter in central analgesia.展开更多
Primary porcine tracheal epithelial cells(PTECs) are an appropriate model for studying the molecular mechanism of various porcine respiratory diseases, including swine-origin mycoplasmas, which are isolated from respi...Primary porcine tracheal epithelial cells(PTECs) are an appropriate model for studying the molecular mechanism of various porcine respiratory diseases, including swine-origin mycoplasmas, which are isolated from respiratory tract of pigs and mainly found on the mucosal surface surrounding swine trachea. However, the short proliferation ability of primary PTECs greatly limits their lifespan. In this study, primary PTECs were carefully isolated and cultured, and immortal PTECs were constructed by transfecting primary PTECs with the recombinant constructed plasmid pEGFPhTERT containing human telomerase reverse transcriptase(hTERT). Immortal PTECs(hTERT-PTECs) maintained both the morphological and functional characteristics of primary PTECs, as indicated by the expression of cytokeratin 18, cellcycle analysis, proliferation assay, Western blotting, telomerase activity assay, karyotype analysis and quantitative RTPCR. Compared to primary PTECs, hTERT-PTECs had an extended replicative lifespan, higher telomerase activity, and enhanced proliferative activity. In addition, this cell line resulted in a lack of transformed and grown tumors in nude mice, suggesting that it could be safely applied in further studies. Moreover, hTERT-PTECs were vulnerable to all swineorigin mycoplasmas through quantitative analysis as indicated by 50% color changing unit(CCU_(50)) calculation, and no significant differences of adhesion ability between primary and immortal PTECs were observed. For the representative swine mycoplasma Mycoplasma hyopneumoniae(Mhp), except for DNA copies quantitative real-time PCR assay, indirect immunofluorescence assay and Western blotting analysis also depicted that hTERT-PTECs was able to adhere to different Mhp strains of different virulence. In summary, like primary PTECs, hTERT-PTECs could be widely used as an adhesion cell model for swine-origin mycoplasmas and in infection studies of various porcine respiratory pathogens.展开更多
Objective To study the audition and inner ear structure in a normal swine model.Methods Auditory brainstem responses(ABRs) were determined in swine at 1 day and 1 month after birth.The form of the cochlea and hair cel...Objective To study the audition and inner ear structure in a normal swine model.Methods Auditory brainstem responses(ABRs) were determined in swine at 1 day and 1 month after birth.The form of the cochlea and hair cells were examined under a scanning electron microscope and on cochlear slices.Results ABR thresholds at 1 day and 1 month post-birth were between 40 and 50 dB SPL.The latencies of waves I,III and V in 1 day old swine were 1.97 ± 0.13,3.01± 0.16 and 4.26±0.20 ms,respectively.At 1 month,the lantancies of waves I,III and V were 2.01 ± 0.05,3.11±0.08 and 4.65 ± 0.14 ms,respectively,slightly longer than those at 1 day,although not statistically significant(p>0.05).The swine cochlea was constituted of 3 and a half turns and the cochlear hair cells lined up in four rows.Hair cell cilia in the apical turn were longer than those in other turns.Conclusions The swine cochlea is mature at the time of birth.Swine ABR thresholds are slightly higher than humans and rats.Swine appears to be a precocial animal species.展开更多
The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized tha...The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.展开更多
Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Ar...Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
This article elucidates the concept of large model technology,summarizes the research status of large model technology both domestically and internationally,provides an overview of the application status of large mode...This article elucidates the concept of large model technology,summarizes the research status of large model technology both domestically and internationally,provides an overview of the application status of large models in vertical industries,outlines the challenges and issues confronted in applying large models in the oil and gas sector,and offers prospects for the application of large models in the oil and gas industry.The existing large models can be briefly divided into three categories:large language models,visual large models,and multimodal large models.The application of large models in the oil and gas industry is still in its infancy.Based on open-source large language models,some oil and gas enterprises have released large language model products using methods like fine-tuning and retrieval augmented generation.Scholars have attempted to develop scenario-specific models for oil and gas operations by using visual/multimodal foundation models.A few researchers have constructed pre-trained foundation models for seismic data processing and interpretation,as well as core analysis.The application of large models in the oil and gas industry faces challenges such as current data quantity and quality being difficult to support the training of large models,high research and development costs,and poor algorithm autonomy and control.The application of large models should be guided by the needs of oil and gas business,taking the application of large models as an opportunity to improve data lifecycle management,enhance data governance capabilities,promote the construction of computing power,strengthen the construction of“artificial intelligence+energy”composite teams,and boost the autonomy and control of large model technology.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these me...To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.展开更多
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the ...Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.展开更多
Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive...Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive disintegration and kinematics of multi-deformable rock blocks during rockslides.The present study proposes a discrete-continuous numerical model,based on a cohesive zone model,to explicitly incorporate the progressive fragmentation and intricate interparticle interactions inherent in rockslides.Breakable rock granular assemblies are released along an inclined plane and flow onto a horizontal plane.The numerical scenarios are established to incorporate variations in slope angle,initial height,friction coefficient,and particle number.The evolutions of fragmentation,kinematic,runout and depositional characteristics are quantitatively analyzed and compared with experimental and field data.A positive linear relationship between the equivalent friction coefficient and the apparent friction coefficient is identified.In general,the granular mass predominantly exhibits characteristics of a dense granular flow,with the Savage number exhibiting a decreasing trend as the volume of mass increases.The process of particle breakage gradually occurs in a bottom-up manner,leading to a significant increase in the angular velocities of the rock blocks with increasing depth.The simulation results reproduce the field observations of inverse grading and source stratigraphy preservation in the deposit.We propose a disintegration index that incorporates factors such as drop height,rock mass volume,and rock strength.Our findings demonstrate a consistent linear relationship between this index and the fragmentation degree in all tested scenarios.展开更多
Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing c...Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.展开更多
In the field of natural language processing(NLP),there have been various pre-training language models in recent years,with question answering systems gaining significant attention.However,as algorithms,data,and comput...In the field of natural language processing(NLP),there have been various pre-training language models in recent years,with question answering systems gaining significant attention.However,as algorithms,data,and computing power advance,the issue of increasingly larger models and a growing number of parameters has surfaced.Consequently,model training has become more costly and less efficient.To enhance the efficiency and accuracy of the training process while reducing themodel volume,this paper proposes a first-order pruningmodel PAL-BERT based on the ALBERT model according to the characteristics of question-answering(QA)system and language model.Firstly,a first-order network pruning method based on the ALBERT model is designed,and the PAL-BERT model is formed.Then,the parameter optimization strategy of the PAL-BERT model is formulated,and the Mish function was used as an activation function instead of ReLU to improve the performance.Finally,after comparison experiments with traditional deep learning models TextCNN and BiLSTM,it is confirmed that PALBERT is a pruning model compression method that can significantly reduce training time and optimize training efficiency.Compared with traditional models,PAL-BERT significantly improves the NLP task’s performance.展开更多
基金supported by Guangzhou Science and Technology Planning Project(2023A04J0131)Special fund for scientific innovation strategyconstruction of high level Academy of Agriculture Science(R2020PY-JG009,R2022PY-QY007,202106TD)+2 种基金China Agriculture Research System-CARS-35the Project of Swine Innovation Team in Guangdong Modern Agricultural Research System(2022KJ126)Special Fund for Rural Revitalization Strategy of Guangdong(2023TS-3),China。
文摘Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.
基金This study was supported by the National Natural Science Foundation of China(72073131)the Central Public-Interest Scientific Institution Basal Research Fund,China(2020JKY025)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2016-AII).
文摘African swine fever(ASF),a fatal disease outbroken in China in August 2018,has widely attracted social concern especially in the information era.The occurrence of ASF led to an imbalance between supply and demand in pork and other meat markets.As a result,meat prices fluctuated greatly during the past year in 2019.To measure ASF quantitatively,the internet public concern index about ASF was created using web crawler methods.The relationships between ASF and meat prices were analyzed based on time-varying parameter vector auto-regressive(TVP-VAR)model.The results showed that there were some differences in the impact size,direction and duration of ASF on the prices of pork,chicken,beef and mutton,and the characteristics of time variability and heterogeneity were obvious.At the same time,the impact of ASF on meat prices is not consistent with the trend and degree of ASF.The impulse intensity is strongly correlated with the strength and duration of ASF,and it is generally weak in the early stage and much stronger in the middle and late periods.The results indicate that macro regulations,monitoring and early-warning system,standardizing production and circulation,and the public opinion monitoring and guidance about ASF should be given more attention in future to stabilize the market expectations and to promote a smooth functioning of the livestock markets.
文摘Objective: To establish a swine model of orthotopic liver transplantation (OLT) which has high standardization, superior reproducibility and stability. Methods: The rate of success, reproducibility and stability were investigated on the modification of OLTs in closed miniature swine with series of improvements. Results: 20 OLTs were performed on the basis of improvements in experimental animals, surgical procedures and operative monitorings. The mean operation time and anhepatic phase was (181±25.8) and (28.4±3.2) min respectively, which were significantly shorter than those of the previous reports. Liver function of the animals recovered shortly after operation. One-week survival rate was 90%, and 15 animals survived more than 1 month. The incidence of vascular and biliary complications was lower in animals with long-term survival. Conclusion: The improved animal model of OLTs in swine is easy to operate with high standardization and rate of success, superior reproducibility and stability. It is an ideal model for series studies related to liver transplantation in big animals.
基金Natural Science Found of Jiangsu Province(BK20171500,16KJB320003)Program for Key disease of Jiangsu Province Science and Technology Department(BL2014088)+1 种基金Program for Innovative Medical Research Team of Jiangsu Province(CXTDA2017007)Jiangsu Province’s key provincial talents program(QNRC2016597).
文摘BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.
文摘Objective To establish the mitral regurgitation swine model and study the change of hydrogen sulfide(H2S)system in chronic heart failure model.Methods Miniature pigs were randomly divided into two groups,the control group(n=6)and mitral regurgitation group(n=6).Chronic heart failure models were established by pulling mitral chordal through a small incision extracorporeal.
基金supported by the Bio&Medical Technology Development Program and Basic Science Research Program through the National Research Foundation(NRF),funded by the Korean government(MSIT)(No.2018M3A9E2024584)the Ministry of Trade,Industry and Energy(MOTIE)and Korea Institute for Advancement of Technology(KIAT)through the International Cooperative R&D program(No.P0011282).
文摘Reproducibility of clinical output is important when investigating therapeutic efficacy in pre-clinical animal studies.Due to its physiological relevance,a swine myocardial infarction(MI)model has been widely used to evaluate the effectiveness of stem cells or tissue-engineered constructs for ischemic heart diseases.Several methods are used to induce MI in the swine model.However,it is difficult,using these approaches,to obtain a similar level of functional outcomes from a group of animals due to interpersonal variation,leading to increased experimental cost.Hence,in order to minimize human intervention,we developed an approach to use a customized occluder that has dimensional similarities with that of the coronary artery of animals in the case of the swine model.We carried out angiography to measure the diameter of the middle left anterior descending artery of each individual animal to fabricate the customized occluder using a 3D-printing system.The fabricated occluder contained a central hole smaller than that of the targeted middle left anterior descending artery to mimic an atherosclerotic coronary artery that has an approximately 20%blocked condition.Interestingly,the 3D-printed occluder can provide continuous blood flow through the central pore,indicating a high survival rate(88%)of up to 28 days post-operation.This method showed the possibility of creating consistent myocardial infarction induction as compared to the conventional representative closed-chest method(50%survival rate),thus highlighting how our method can have a profound effect on accelerating reliable experiments for developing new therapeutic approaches to ischemic heart diseases.
基金the National Natural Science Foundation of China,No. 3047051530570480
文摘BACKGROUND: In localized brain proton magnetic resonance spectroscopy (^1H-MRS), metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which is assumed to be stable in normal, as well as many pathological, states. However, in vivo creatine levels do not remain constant. Therefore, absolute metabolite measurements, which provide the precise concentrations of certain chemical compounds, are superior to metabolite ratios for determining pathological and evolutional changes. OBJECTIVE: To investigate the feasibility of quantification analysis of brain metabolite changes caused by central analgesics nasal spray using the ^1H-MRS and linear combination model (LCModel) methods. DESIGN, TIME AND SETTING: This neuroimaging, observational, animal study was performed at the Laboratory of the Department of Medical Imaging, Second Affiliated Hospital, Medical College, Shantou University, China from July to December 2007. MATERIALS: Butorphanol tartrate nasal spray, as a mixed agonist-antagonist opioid analgesic, was purchased from Shanghai Hengrui Pharmacy, China. A General Electric Signa 1.5T System (General Electric Medical Systems, Milwaukee, WI, USA) and LCModel software (Stephen Provencher, Oakville, Ontario, Canada) were used in this study. METHODS: MRS images were acquired in ten healthy swine aged 2 weeks using single-voxel point-resolved spectroscopic sequence. A region of interest (2 cm × 2 cm × 2 cm) was placed in the image centers of maximum brain parenchyma. Repeated MRS scanning was performed 15-20 minutes after intranasal administration of 1 mg of butorphanol tartrate. Three settings of repetition time/echo time were selected before and after nasal spray administration 3 000 ms/30 ms,1 500 ms/30 ms, and 3 000 ms/50 ms. Metabolite concentrations were estimated by LCModel software. MAIN OUTCOME MEASURES: ^1H-MRS spectra was obtained using various repetition time/echo time settings. Concentrations of glutamate compounds (glutamate + glutamine), N-acetyl aspartate, and choline were detected in swine brain prior to and following nasal spray treatment. RESULTS: The glutamate compounds curve was consistent with original spectra, when a repetition time/echo time of 3 000 ms/30 ms was adopted. Concentrations of glutamate compounds, N-acetyl aspartate, and choline decreased following administration. The most significant reduction was observed in glutamate compound concentrations from (9.28 ± 0.54) mmol/kg to (7.28 ± 0.54) mmol/kg (P 〈 0.05). CONCLUSION: ^1H-MRS and LCModel software were effectively utilized to quantitatively analyze and measure brain metabolites. Glutamate compounds might be an important neurotransmitter in central analgesia.
基金supported by the National Natural Science Foundation of China(31800161,31700157,31800160,31900159,and 31770193)the Natural Science Foundation of Jiangsu Province,China(BK20180297 and BK20170600)the Independent Research Project Program of Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base,Ministry of Science and Technology,China(2019sy004)。
文摘Primary porcine tracheal epithelial cells(PTECs) are an appropriate model for studying the molecular mechanism of various porcine respiratory diseases, including swine-origin mycoplasmas, which are isolated from respiratory tract of pigs and mainly found on the mucosal surface surrounding swine trachea. However, the short proliferation ability of primary PTECs greatly limits their lifespan. In this study, primary PTECs were carefully isolated and cultured, and immortal PTECs were constructed by transfecting primary PTECs with the recombinant constructed plasmid pEGFPhTERT containing human telomerase reverse transcriptase(hTERT). Immortal PTECs(hTERT-PTECs) maintained both the morphological and functional characteristics of primary PTECs, as indicated by the expression of cytokeratin 18, cellcycle analysis, proliferation assay, Western blotting, telomerase activity assay, karyotype analysis and quantitative RTPCR. Compared to primary PTECs, hTERT-PTECs had an extended replicative lifespan, higher telomerase activity, and enhanced proliferative activity. In addition, this cell line resulted in a lack of transformed and grown tumors in nude mice, suggesting that it could be safely applied in further studies. Moreover, hTERT-PTECs were vulnerable to all swineorigin mycoplasmas through quantitative analysis as indicated by 50% color changing unit(CCU_(50)) calculation, and no significant differences of adhesion ability between primary and immortal PTECs were observed. For the representative swine mycoplasma Mycoplasma hyopneumoniae(Mhp), except for DNA copies quantitative real-time PCR assay, indirect immunofluorescence assay and Western blotting analysis also depicted that hTERT-PTECs was able to adhere to different Mhp strains of different virulence. In summary, like primary PTECs, hTERT-PTECs could be widely used as an adhesion cell model for swine-origin mycoplasmas and in infection studies of various porcine respiratory pathogens.
基金supported by a Natural Science Foundation of China(NSFC) grant to 863: 2007AA02Z150 general program Natioual natural scienle foundation of China:30871398Key proiects in the national science & technology pillar program during me elevench five year plan period:2008BAI50B08,key profram of Natural Scievne foundation of China:30730040
文摘Objective To study the audition and inner ear structure in a normal swine model.Methods Auditory brainstem responses(ABRs) were determined in swine at 1 day and 1 month after birth.The form of the cochlea and hair cells were examined under a scanning electron microscope and on cochlear slices.Results ABR thresholds at 1 day and 1 month post-birth were between 40 and 50 dB SPL.The latencies of waves I,III and V in 1 day old swine were 1.97 ± 0.13,3.01± 0.16 and 4.26±0.20 ms,respectively.At 1 month,the lantancies of waves I,III and V were 2.01 ± 0.05,3.11±0.08 and 4.65 ± 0.14 ms,respectively,slightly longer than those at 1 day,although not statistically significant(p>0.05).The swine cochlea was constituted of 3 and a half turns and the cochlear hair cells lined up in four rows.Hair cell cilia in the apical turn were longer than those in other turns.Conclusions The swine cochlea is mature at the time of birth.Swine ABR thresholds are slightly higher than humans and rats.Swine appears to be a precocial animal species.
基金supported in part by the NIH grant R01CA241134supported in part by the NSF grant CMMI-1552764+3 种基金supported in part by the NSF grants DMS-1349724 and DMS-2052465supported in part by the NSF grant CCF-1740761supported in part by the U.S.-Norway Fulbright Foundation and the Research Council of Norway R&D Grant 309273supported in part by the Norwegian Centennial Chair grant and the Doctoral Dissertation Fellowship from the University of Minnesota.
文摘The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.
基金supported by the Chinese–Norwegian Collaboration Projects within Climate Systems jointly funded by the National Key Research and Development Program of China (Grant No.2022YFE0106800)the Research Council of Norway funded project,MAPARC (Grant No.328943)+2 种基金the support from the Research Council of Norway funded project,COMBINED (Grant No.328935)the National Natural Science Foundation of China (Grant No.42075030)the Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX23_1314)。
文摘Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金Supported by the National Natural Science Foundation of China(72088101,42372175)PetroChina Science and Technology Innovation Fund Program(2021DQ02-0904)。
文摘This article elucidates the concept of large model technology,summarizes the research status of large model technology both domestically and internationally,provides an overview of the application status of large models in vertical industries,outlines the challenges and issues confronted in applying large models in the oil and gas sector,and offers prospects for the application of large models in the oil and gas industry.The existing large models can be briefly divided into three categories:large language models,visual large models,and multimodal large models.The application of large models in the oil and gas industry is still in its infancy.Based on open-source large language models,some oil and gas enterprises have released large language model products using methods like fine-tuning and retrieval augmented generation.Scholars have attempted to develop scenario-specific models for oil and gas operations by using visual/multimodal foundation models.A few researchers have constructed pre-trained foundation models for seismic data processing and interpretation,as well as core analysis.The application of large models in the oil and gas industry faces challenges such as current data quantity and quality being difficult to support the training of large models,high research and development costs,and poor algorithm autonomy and control.The application of large models should be guided by the needs of oil and gas business,taking the application of large models as an opportunity to improve data lifecycle management,enhance data governance capabilities,promote the construction of computing power,strengthen the construction of“artificial intelligence+energy”composite teams,and boost the autonomy and control of large model technology.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
基金supported by University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金We acknowledge funding from NSFC Grant 62306283.
文摘Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.
基金support from the National Key R&D plan(Grant No.2022YFC3004303)the National Natural Science Foundation of China(Grant No.42107161)+3 种基金the State Key Laboratory of Hydroscience and Hydraulic Engineering(Grant No.2021-KY-04)the Open Research Fund Program of State Key Laboratory of Hydroscience and Engineering(sklhse-2023-C-01)the Open Research Fund Program of Key Laboratory of the Hydrosphere of the Ministry of Water Resources(mklhs-2023-04)the China Three Gorges Corporation(XLD/2117).
文摘Rock fragmentation plays a critical role in rock avalanches,yet conventional approaches such as classical granular flow models or the bonded particle model have limitations in accurately characterizing the progressive disintegration and kinematics of multi-deformable rock blocks during rockslides.The present study proposes a discrete-continuous numerical model,based on a cohesive zone model,to explicitly incorporate the progressive fragmentation and intricate interparticle interactions inherent in rockslides.Breakable rock granular assemblies are released along an inclined plane and flow onto a horizontal plane.The numerical scenarios are established to incorporate variations in slope angle,initial height,friction coefficient,and particle number.The evolutions of fragmentation,kinematic,runout and depositional characteristics are quantitatively analyzed and compared with experimental and field data.A positive linear relationship between the equivalent friction coefficient and the apparent friction coefficient is identified.In general,the granular mass predominantly exhibits characteristics of a dense granular flow,with the Savage number exhibiting a decreasing trend as the volume of mass increases.The process of particle breakage gradually occurs in a bottom-up manner,leading to a significant increase in the angular velocities of the rock blocks with increasing depth.The simulation results reproduce the field observations of inverse grading and source stratigraphy preservation in the deposit.We propose a disintegration index that incorporates factors such as drop height,rock mass volume,and rock strength.Our findings demonstrate a consistent linear relationship between this index and the fragmentation degree in all tested scenarios.
基金the financial support provided by the National Natural Science Foundation of China(Grant No.42272310).
文摘Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.
基金Supported by Sichuan Science and Technology Program(2021YFQ0003,2023YFSY0026,2023YFH0004).
文摘In the field of natural language processing(NLP),there have been various pre-training language models in recent years,with question answering systems gaining significant attention.However,as algorithms,data,and computing power advance,the issue of increasingly larger models and a growing number of parameters has surfaced.Consequently,model training has become more costly and less efficient.To enhance the efficiency and accuracy of the training process while reducing themodel volume,this paper proposes a first-order pruningmodel PAL-BERT based on the ALBERT model according to the characteristics of question-answering(QA)system and language model.Firstly,a first-order network pruning method based on the ALBERT model is designed,and the PAL-BERT model is formed.Then,the parameter optimization strategy of the PAL-BERT model is formulated,and the Mish function was used as an activation function instead of ReLU to improve the performance.Finally,after comparison experiments with traditional deep learning models TextCNN and BiLSTM,it is confirmed that PALBERT is a pruning model compression method that can significantly reduce training time and optimize training efficiency.Compared with traditional models,PAL-BERT significantly improves the NLP task’s performance.