AIM： To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS： A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomograp...AIM： To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS： A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography （CT） and magnetic resonance imaging （MRI） were used to observe tumorgrowth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded.RESULTS： Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density loci of the tumor in the rectum wail, while enhanced CT scanning demonstrated a symmetrical intensification in tumor loci. MRI scanning showed alow signal of the tumor on T1-weighted imaging anda high signal of the tumor on T2-weighted imaging.Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could beobserved 6 wk after VX2 cell implantation, and a largearea of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation.CONCLUSION： The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.展开更多
Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way. Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensio...Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way. Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensions or tumor mass suspensions were injected into breast tissues of rabbits of group A and B, respectively. Tumor blocks were surgically implanted in rabbit breasts of group C. Tumor formation rate, tumor growth rate, and tumor-bearing survival time was compared, and the histological feature of tumor was observed. Results: Models were established conveniently and successfully in rabbits received injection of tumor mass suspensions. Tumor proliferated rapidly with the biological feature of squamous cell carcinoma. Conclusion: VX2 breast carcinoma model in rabbit was established successfully. Intramammary injection of tumor mass suspension is the best method.展开更多
Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experime...Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.展开更多
AIM： To establish models of portal vein occlusion of hepatic VX2 tumor in rabbits and to evaluate the value of multi-slice CT. METHODS： Forty New Zealand rabbits were divided into 4 groups according to digital table...AIM： To establish models of portal vein occlusion of hepatic VX2 tumor in rabbits and to evaluate the value of multi-slice CT. METHODS： Forty New Zealand rabbits were divided into 4 groups according to digital table： Immediate group （group A; transplantation of tumor immediately after the portal vein occlusion）, 3-wk group （group B; transplantation of tumor at 3 wk after the portal vein occlusion）, negative control group （group C） and positive control group （group D）, 10 rabbits in each group. Hepatic VX2 tumor was transplanted with abdominalembedding innoculation immediately after the portal vein occlusion and at 3 wk after the portal vein occlusion. Meanwhile, they were divided into negative control group （Left external branch of portal vein was occluded by sham-operation, and left exite was embedded and inoculated pseudoly） and positive control group （Transplanted tumor did not suffer from the portal vein occlusion）. All rabbits were scanned with multi-slice CT. RESULTS： All 40 animals were employed in the final analysis without death. Tumor did not grow in both immediate group and 3-wk group. In 3-wk group, left endite was atrophied and growth of tumor was inhibited. The maximal diameter of tumor was significantly smaller than that in positive control group （2.55±0.46 vs 3.59±0.37 cm, t = 5.57, P 〈 0.001）. Incidences of metastasis in the liver and lung were lower in 3-wk group than those in positive control group （10% vs 400, and 90% vs 100%, respectively）. The expression intensities of the vascular endothelium growth factor （VEGF） in groups A, B, C and D were 0.10±0.06, 0.66±0.21, 0.28±0.09 and 1.48±0.32, respectively. VEGF expression level in the test group A was significantly lower than that in the negative control group C （t = 5.07; P 〈 0.001）.In addition, VEGF expression in the test group B was significantly lower than that in the positive control group D （t = 6.38; P 〈 0.001）. Scanning with multi-slice CT showed that displaying rate of hepatic artery branches was obviously lower in grade Ⅲ（40%） than that in grade Ⅰ（70%） and Ⅱ（100%） （P 〈 0.05）; but there was no significant difference in displaying rate of the portal vein at various grades. Values of blood flow （BF） of the liver, blood volume （BV）, mean transit time （MTT） and permeability of vascular surface （PS） were lower in the immediate group and 3-wk group than those in control groups, but values of hepatic arterial fraction （HAF） were increased. Significant positive correlations were existed between BF and BV （r = 0.905, P 〈 0.01）, and between BF and PS （r = 0.967, P 〈 0.01）, between BV and PS （r = 0.889, P 〈 0.01）. A significant negative correlation existed between PV and HAF （r = -0.768, P 〈 0.01）, between PS and HAF （r = -0.557, P 〈 0.01）. The values of BF, BV and PS had a positive correlation with VEGF （rBF = 0.842, rBV = 0.579, rPS = 0.811, P 〈 0.01） . However, there was no significant correlation between the values of MTT and HAF and the VEGF expression （rMTt = 0.066, rHAF = -0.027）. CONCLUSION： Ligating the left external branch of portal vein is an ideal way to establish models of portal vein occlusion in rabbits with hepatic VX2 tumor. Multi slice CT plays a key role in evaluating effect of portal vein occlusion.展开更多
AIM:To compare two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma.METHODS:Thirty New Zealand rabbits were randomly divided into two groups:A and B.Group A was assigned a traditional laparotomy me...AIM:To compare two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma.METHODS:Thirty New Zealand rabbits were randomly divided into two groups:A and B.Group A was assigned a traditional laparotomy method(embedding tumor fragments directly into the liver with tweezers).Group B was subjected to an improved laparotomy method(injection of tumor fragments into the liver through a 15 G syringe needle).The operation time, incision length, incision infection rate, and mortality rate were compared between the two groups after laparotomy.Magnetic resonance imaging(MRI) was performed to evaluate tumor formation rates and the characteristics of the tumors 2 wk after laparotomy.RESULTS:The mean operation times for the two groups(Group A vs Group B) were 23.2 ± 3.4 min vs 17.5 ± 2.9 min(P < 0.05); the incision length was 3.3 ± 0.5 cm vs 2.4 ± 0.6 cm(P < 0.05); and the mortality rate after 2 wk was 26.7% vs 0%(P < 0.05); all of these outcomes were significantly different between the two groups.The incision infection rates in the two groups were 6.7% vs 0%(P > 0.05), whichwere not significantly different.MRI performed after 2weeks showed that the tumor formation rates in the two groups were 90.9%vs 93.3%(P>0.05).These rates were not significantly different between the two groups.The celiac implantation rate and abdominal wall metastasis rate in the two groups were 36.4%vs 13.3%(P<0.05)and 27.2%vs 6.7%(P<0.05),respectively,which were significantly different between the two groups.CONCLUSION:The tumor formation rates were not significantly different between the two methods for modeling rabbit VX2 hepatocarcinoma.However,the improved method is recommended because it has certain advantages.展开更多
The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography.VX2 tumor fragments were implant...The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography.VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography.Conventional ultrasonography and contrast-enhanced ultrasonography(CEUS)were performed 14 days after inoculation,and then the rabbits were sacrificed and pathologically examined.The success rate of inoculation was 100%.The average size of liver VX2 tumor was 1.7 cm×1.3 cm,CEUS of VX2 liver tumors showed the"rapid wash-in and wash-out"vascular pattern.There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A,k and A×k(P<0.05),which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma.Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor.And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.展开更多
OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effe...OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.展开更多
Objective:This study aimed to analyze the effects of transcatheter arterial embolization(TAE)combined with portal venous embolization(PVE)on the expression of MMP-2 in residual VX2 liver tumor tissues,liver function a...Objective:This study aimed to analyze the effects of transcatheter arterial embolization(TAE)combined with portal venous embolization(PVE)on the expression of MMP-2 in residual VX2 liver tumor tissues,liver function and non-embolic lobe regeneration.Methods:A total of 72 rabbits were randomly divided into Sham,TAE,PVE and TAE+PVE groups(n=18/group).The tissue samples from each group were taken at 6 h,3 days and 7 days after interventional operation,respectively.MMP-2 expression was detected by immunohistochemistry,Real-time PCR,and Western-blotting.The main indicators(such as AST,ATL,and TBIL)of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation.One-way ANOVA and Kruskal-wallis method were used for statistical analysis.Results:The expression of MMP-2 mRNA and protein remained the highest in the Sham group,and the expression of MMP-2 mRNA and protein in TAE,PVE and TAE+PVE groups were successively increased,and the expression of MMP-2 in TAE+PVE group was always significantly higher than TAE group.The AST and ALT levels in each group on day 7 after operation showed a significant declination,and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference.On day 7 after operation,the increasing volume of non-embolized liver lobes in TAE+PVE group showed a more significant effect than those in PVE group,but there was no statistical significance(37.62±1.54 ml VS 36.18±1.15 ml,P=0.881),and its volume was significantly higher than those in the sham group(27.03±1.11 ml).Conclusion:TAE+PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor,but the expression of MMP-2 increased fastest after TAE+PVE,which might promote tumor cell invasion and metastasis.展开更多
Current shipping,tourism,and resource development requirements call for more accurate predictions of the Arctic sea-ice concentration(SIC).However,due to the complex physical processes involved,predicting the spatiote...Current shipping,tourism,and resource development requirements call for more accurate predictions of the Arctic sea-ice concentration(SIC).However,due to the complex physical processes involved,predicting the spatiotemporal distribution of Arctic SIC is more challenging than predicting its total extent.In this study,spatiotemporal prediction models for monthly Arctic SIC at 1-to 3-month leads are developed based on U-Net-an effective convolutional deep-learning approach.Based on explicit Arctic sea-ice-atmosphere interactions,11 variables associated with Arctic sea-ice variations are selected as predictors,including observed Arctic SIC,atmospheric,oceanic,and heat flux variables at 1-to 3-month leads.The prediction skills for the monthly Arctic SIC of the test set(from January 2018 to December 2022)are evaluated by examining the mean absolute error(MAE)and binary accuracy(BA).Results showed that the U-Net model had lower MAE and higher BA for Arctic SIC compared to two dynamic climate prediction systems(CFSv2 and NorCPM).By analyzing the relative importance of each predictor,the prediction accuracy relies more on the SIC at the 1-month lead,but on the surface net solar radiation flux at 2-to 3-month leads.However,dynamic models show limited prediction skills for surface net solar radiation flux and other physical processes,especially in autumn.Therefore,the U-Net model can be used to capture the connections among these key physical processes associated with Arctic sea ice and thus offers a significant advantage in predicting Arctic SIC.展开更多
Cyberbullying on social media poses significant psychological risks,yet most detection systems over-simplify the task by focusing on binary classification,ignoring nuanced categories like passive-aggressive remarks or...Cyberbullying on social media poses significant psychological risks,yet most detection systems over-simplify the task by focusing on binary classification,ignoring nuanced categories like passive-aggressive remarks or indirect slurs.To address this gap,we propose a hybrid framework combining Term Frequency-Inverse Document Frequency(TF-IDF),word-to-vector(Word2Vec),and Bidirectional Encoder Representations from Transformers(BERT)based models for multi-class cyberbullying detection.Our approach integrates TF-IDF for lexical specificity and Word2Vec for semantic relationships,fused with BERT’s contextual embeddings to capture syntactic and semantic complexities.We evaluate the framework on a publicly available dataset of 47,000 annotated social media posts across five cyberbullying categories:age,ethnicity,gender,religion,and indirect aggression.Among BERT variants tested,BERT Base Un-Cased achieved the highest performance with 93%accuracy(standard deviation across±1%5-fold cross-validation)and an average AUC of 0.96,outperforming standalone TF-IDF(78%)and Word2Vec(82%)models.Notably,it achieved near-perfect AUC scores(0.99)for age and ethnicity-based bullying.A comparative analysis with state-of-the-art benchmarks,including Generative Pre-trained Transformer 2(GPT-2)and Text-to-Text Transfer Transformer(T5)models highlights BERT’s superiority in handling ambiguous language.This work advances cyberbullying detection by demonstrating how hybrid feature extraction and transformer models improve multi-class classification,offering a scalable solution for moderating nuanced harmful content.展开更多
The identification and optimization of mutations in nanobodies are crucial for enhancing their thera-peutic potential in disease prevention and control.However,this process is often complex and time-consuming,which li...The identification and optimization of mutations in nanobodies are crucial for enhancing their thera-peutic potential in disease prevention and control.However,this process is often complex and time-consuming,which limit its widespread application in practice.In this study,we developed a work-flow,named Evolutionary-Nanobody(EvoNB),to predict key mutation sites of nanobodies by combining protein language models(PLMs)and molecular dynamic(MD)simulations.By fine-tuning the ESM2 model on a large-scale nanobody dataset,the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced.The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies.Additionally,we selected four widely representative nanobodyeantigen complexes to verify the predicted effects of mutations.MD simulations analyzed the energy changes caused by these mu-tations to predict their impact on binding affinity to the targets.The results showed that multiple mu-tations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target,further validating the potential of this workflow for designing and optimizing nanobody mutations.Additionally,sequence-based predictions are generally less dependent on structural absence,allowing them to be more easily integrated with tools for structural predictions,such as AlphaFold 3.Through mutation prediction and systematic analysis of key sites,we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes.The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.展开更多
Characterized by special morphologic,geographic,hydrologic,and societal behaviors,the water resources management of the Mediterranean catchment often shows a higher level of complexity including security issues of wat...Characterized by special morphologic,geographic,hydrologic,and societal behaviors,the water resources management of the Mediterranean catchment often shows a higher level of complexity including security issues of water supply,inundation risks,and environment management under the perspective of climate change.To have a comprehensive understanding of the Mediterranean water-cycle system,a deterministic distributed hydrologic modeling approach has been developed and presented in this study based on an application in the Var catchment(2800 km^(2))located at the French Mediterranean region.A 1D and 2D coupled model of MIKE SHE and MIKE 11 has been set up under a series of hypotheses to represent the whole hydrologic and hydrodynamic processes including rainfall-runoff,snow-melting,channel flow,overland flow,and the water exchange between land surface and unsaturated/saturated zones.The developed model was first calibrated with 4 years daily records from 2008 to 2011,then to be validated and further run within hourly time interval to produce detailed representation of the catchment water-cycle from 2012 to 2014.The deterministic distributed modeling approach presented in this study is able to represent its complicated water-cycle and used for supporting the decision‐making process of the water resources management of the catchment.展开更多
Radio frequency capacitively coupled plasmas(RF CCPs)operated in Ar/O_(2)gas mixtures which are widely adopted in microelectronics,display,and photovoltaic industry,are investigated based on an equivalent circuit mode...Radio frequency capacitively coupled plasmas(RF CCPs)operated in Ar/O_(2)gas mixtures which are widely adopted in microelectronics,display,and photovoltaic industry,are investigated based on an equivalent circuit model coupled with a global model.This study focuses on the effects of singlet metastable molecule O_(2)(b^(1)∑_(8)^(+)),highly excited Herzberg states O_(2)(A^(3)∑_(u)^(+),A^(3)△_(u),c^(1)∑_(u)^(-)),and the negative ion O_(2)^(-),which are usually neglected in simulation studies.Specifically,their impact on particle densities,electronegativity,electron temperature,voltage drop across the sheath,and absorbed power in the discharge is analyzed.The results indicate that O_(2)(b^(1)∑_(8)^(+))and O_(2)^(-)exhibit relatively high densities in argon-oxygen discharges.While O_(2)(A^(3)∑_(u)^(+),A^(3)△_(u),c^(1)∑_(u)^(-))play a critical role in O_(2)b1S+g production,especially at higher pressure.The inclusion of these particles reduces the electronegativity,electron temperature,and key species densities,especially the O^(-)and O^(*)densities.Moreover,the sheath voltage drop,as well as the inductance and resistance of the plasma bulk are enhanced,while the sheath dissipation power and total absorbed power decrease slightly.With the increasing pressure,the influence of these particles on the discharge properties becomes more significant.The study also explores the generation and loss of main neutral species and charged particles within the pressure range of 20 mTorr-100 mTorr(1 Torr=1.33322×10^(2)Pa),offering insights into essential and non-essential reactions for future low-pressure O_(2)and Ar/O_(2)CCP discharge modeling.展开更多
The objective of this work is to develop an innovative system(ROSGPT)that merges large language models(LLMs)with the robot operating system(ROS),facilitating natural language voice control of mobile robots.This integr...The objective of this work is to develop an innovative system(ROSGPT)that merges large language models(LLMs)with the robot operating system(ROS),facilitating natural language voice control of mobile robots.This integration aims to bridge the gap between human-robot interaction(HRI)and artificial intelligence(AI).ROSGPT integrates several subsystems,including speech recognition,prompt engineering,LLM and ROS,enabling seamless control of robots through human voice or text commands.The LLM component is optimized,with its performance refined from the open-source Llama2 model through fine-tuning and quantization procedures.Through extensive experiments conducted in both real-world and virtual environments,ROSGPT demonstrates its efficacy in meeting user requirements and delivering user-friendly interactive experiences.The system demonstrates versatility and adaptability through its ability to comprehend diverse user commands and execute corresponding tasks with precision and reliability,thereby showcasing its potential for various practical applications in robotics and AI.The demonstration video can be viewed at https://iklxo6z9yv.feishu.cn/docx/Lux3dmTDxoZ5YnxWJTZcxUCWnTh.展开更多
Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Class...Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC’s generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.展开更多
The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF str...The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction.展开更多
Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion...Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.展开更多
Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune press...Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.展开更多
文摘AIM： To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma.METHODS： A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography （CT） and magnetic resonance imaging （MRI） were used to observe tumorgrowth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded.RESULTS： Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density loci of the tumor in the rectum wail, while enhanced CT scanning demonstrated a symmetrical intensification in tumor loci. MRI scanning showed alow signal of the tumor on T1-weighted imaging anda high signal of the tumor on T2-weighted imaging.Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could beobserved 6 wk after VX2 cell implantation, and a largearea of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation.CONCLUSION： The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.
文摘Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way. Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensions or tumor mass suspensions were injected into breast tissues of rabbits of group A and B, respectively. Tumor blocks were surgically implanted in rabbit breasts of group C. Tumor formation rate, tumor growth rate, and tumor-bearing survival time was compared, and the histological feature of tumor was observed. Results: Models were established conveniently and successfully in rabbits received injection of tumor mass suspensions. Tumor proliferated rapidly with the biological feature of squamous cell carcinoma. Conclusion: VX2 breast carcinoma model in rabbit was established successfully. Intramammary injection of tumor mass suspension is the best method.
基金This work was supported by the National Natural Science Foundation of China (No30371831)
文摘Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.
文摘AIM： To establish models of portal vein occlusion of hepatic VX2 tumor in rabbits and to evaluate the value of multi-slice CT. METHODS： Forty New Zealand rabbits were divided into 4 groups according to digital table： Immediate group （group A; transplantation of tumor immediately after the portal vein occlusion）, 3-wk group （group B; transplantation of tumor at 3 wk after the portal vein occlusion）, negative control group （group C） and positive control group （group D）, 10 rabbits in each group. Hepatic VX2 tumor was transplanted with abdominalembedding innoculation immediately after the portal vein occlusion and at 3 wk after the portal vein occlusion. Meanwhile, they were divided into negative control group （Left external branch of portal vein was occluded by sham-operation, and left exite was embedded and inoculated pseudoly） and positive control group （Transplanted tumor did not suffer from the portal vein occlusion）. All rabbits were scanned with multi-slice CT. RESULTS： All 40 animals were employed in the final analysis without death. Tumor did not grow in both immediate group and 3-wk group. In 3-wk group, left endite was atrophied and growth of tumor was inhibited. The maximal diameter of tumor was significantly smaller than that in positive control group （2.55±0.46 vs 3.59±0.37 cm, t = 5.57, P 〈 0.001）. Incidences of metastasis in the liver and lung were lower in 3-wk group than those in positive control group （10% vs 400, and 90% vs 100%, respectively）. The expression intensities of the vascular endothelium growth factor （VEGF） in groups A, B, C and D were 0.10±0.06, 0.66±0.21, 0.28±0.09 and 1.48±0.32, respectively. VEGF expression level in the test group A was significantly lower than that in the negative control group C （t = 5.07; P 〈 0.001）.In addition, VEGF expression in the test group B was significantly lower than that in the positive control group D （t = 6.38; P 〈 0.001）. Scanning with multi-slice CT showed that displaying rate of hepatic artery branches was obviously lower in grade Ⅲ（40%） than that in grade Ⅰ（70%） and Ⅱ（100%） （P 〈 0.05）; but there was no significant difference in displaying rate of the portal vein at various grades. Values of blood flow （BF） of the liver, blood volume （BV）, mean transit time （MTT） and permeability of vascular surface （PS） were lower in the immediate group and 3-wk group than those in control groups, but values of hepatic arterial fraction （HAF） were increased. Significant positive correlations were existed between BF and BV （r = 0.905, P 〈 0.01）, and between BF and PS （r = 0.967, P 〈 0.01）, between BV and PS （r = 0.889, P 〈 0.01）. A significant negative correlation existed between PV and HAF （r = -0.768, P 〈 0.01）, between PS and HAF （r = -0.557, P 〈 0.01）. The values of BF, BV and PS had a positive correlation with VEGF （rBF = 0.842, rBV = 0.579, rPS = 0.811, P 〈 0.01） . However, there was no significant correlation between the values of MTT and HAF and the VEGF expression （rMTt = 0.066, rHAF = -0.027）. CONCLUSION： Ligating the left external branch of portal vein is an ideal way to establish models of portal vein occlusion in rabbits with hepatic VX2 tumor. Multi slice CT plays a key role in evaluating effect of portal vein occlusion.
基金Supported by Natural Science Foundation of Hunan Province,China,No.14JJ2034Project of the Development and Reform Commission of Hunan Province,China,No.2013-1199Project of the Science and Technology Department of Hunan Province,China,No.2014TT2017
文摘AIM:To compare two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma.METHODS:Thirty New Zealand rabbits were randomly divided into two groups:A and B.Group A was assigned a traditional laparotomy method(embedding tumor fragments directly into the liver with tweezers).Group B was subjected to an improved laparotomy method(injection of tumor fragments into the liver through a 15 G syringe needle).The operation time, incision length, incision infection rate, and mortality rate were compared between the two groups after laparotomy.Magnetic resonance imaging(MRI) was performed to evaluate tumor formation rates and the characteristics of the tumors 2 wk after laparotomy.RESULTS:The mean operation times for the two groups(Group A vs Group B) were 23.2 ± 3.4 min vs 17.5 ± 2.9 min(P < 0.05); the incision length was 3.3 ± 0.5 cm vs 2.4 ± 0.6 cm(P < 0.05); and the mortality rate after 2 wk was 26.7% vs 0%(P < 0.05); all of these outcomes were significantly different between the two groups.The incision infection rates in the two groups were 6.7% vs 0%(P > 0.05), whichwere not significantly different.MRI performed after 2weeks showed that the tumor formation rates in the two groups were 90.9%vs 93.3%(P>0.05).These rates were not significantly different between the two groups.The celiac implantation rate and abdominal wall metastasis rate in the two groups were 36.4%vs 13.3%(P<0.05)and 27.2%vs 6.7%(P<0.05),respectively,which were significantly different between the two groups.CONCLUSION:The tumor formation rates were not significantly different between the two methods for modeling rabbit VX2 hepatocarcinoma.However,the improved method is recommended because it has certain advantages.
文摘The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography.VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography.Conventional ultrasonography and contrast-enhanced ultrasonography(CEUS)were performed 14 days after inoculation,and then the rabbits were sacrificed and pathologically examined.The success rate of inoculation was 100%.The average size of liver VX2 tumor was 1.7 cm×1.3 cm,CEUS of VX2 liver tumors showed the"rapid wash-in and wash-out"vascular pattern.There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A,k and A×k(P<0.05),which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma.Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor.And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.
文摘OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.
基金supported by Natural Science Foundation of Anhui Province(NO.1408085MH162)
文摘Objective:This study aimed to analyze the effects of transcatheter arterial embolization(TAE)combined with portal venous embolization(PVE)on the expression of MMP-2 in residual VX2 liver tumor tissues,liver function and non-embolic lobe regeneration.Methods:A total of 72 rabbits were randomly divided into Sham,TAE,PVE and TAE+PVE groups(n=18/group).The tissue samples from each group were taken at 6 h,3 days and 7 days after interventional operation,respectively.MMP-2 expression was detected by immunohistochemistry,Real-time PCR,and Western-blotting.The main indicators(such as AST,ATL,and TBIL)of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation.One-way ANOVA and Kruskal-wallis method were used for statistical analysis.Results:The expression of MMP-2 mRNA and protein remained the highest in the Sham group,and the expression of MMP-2 mRNA and protein in TAE,PVE and TAE+PVE groups were successively increased,and the expression of MMP-2 in TAE+PVE group was always significantly higher than TAE group.The AST and ALT levels in each group on day 7 after operation showed a significant declination,and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference.On day 7 after operation,the increasing volume of non-embolized liver lobes in TAE+PVE group showed a more significant effect than those in PVE group,but there was no statistical significance(37.62±1.54 ml VS 36.18±1.15 ml,P=0.881),and its volume was significantly higher than those in the sham group(27.03±1.11 ml).Conclusion:TAE+PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor,but the expression of MMP-2 increased fastest after TAE+PVE,which might promote tumor cell invasion and metastasis.
基金supported by the National Key Research and Development Program of China[grant number 2022YFE0106800]an Innovation Group Project of the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)[grant number 311024001]+3 种基金a project supported by the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)[grant number SML2023SP209]a Research Council of Norway funded project(MAPARC)[grant number 328943]a Nansen Center´s basic institutional funding[grant number 342624]the high-performance computing support from the School of Atmospheric Science at Sun Yat-sen University。
文摘Current shipping,tourism,and resource development requirements call for more accurate predictions of the Arctic sea-ice concentration(SIC).However,due to the complex physical processes involved,predicting the spatiotemporal distribution of Arctic SIC is more challenging than predicting its total extent.In this study,spatiotemporal prediction models for monthly Arctic SIC at 1-to 3-month leads are developed based on U-Net-an effective convolutional deep-learning approach.Based on explicit Arctic sea-ice-atmosphere interactions,11 variables associated with Arctic sea-ice variations are selected as predictors,including observed Arctic SIC,atmospheric,oceanic,and heat flux variables at 1-to 3-month leads.The prediction skills for the monthly Arctic SIC of the test set(from January 2018 to December 2022)are evaluated by examining the mean absolute error(MAE)and binary accuracy(BA).Results showed that the U-Net model had lower MAE and higher BA for Arctic SIC compared to two dynamic climate prediction systems(CFSv2 and NorCPM).By analyzing the relative importance of each predictor,the prediction accuracy relies more on the SIC at the 1-month lead,but on the surface net solar radiation flux at 2-to 3-month leads.However,dynamic models show limited prediction skills for surface net solar radiation flux and other physical processes,especially in autumn.Therefore,the U-Net model can be used to capture the connections among these key physical processes associated with Arctic sea ice and thus offers a significant advantage in predicting Arctic SIC.
基金funded by Scientific Research Deanship at University of Hail-Saudi Arabia through Project Number RG-23092.
文摘Cyberbullying on social media poses significant psychological risks,yet most detection systems over-simplify the task by focusing on binary classification,ignoring nuanced categories like passive-aggressive remarks or indirect slurs.To address this gap,we propose a hybrid framework combining Term Frequency-Inverse Document Frequency(TF-IDF),word-to-vector(Word2Vec),and Bidirectional Encoder Representations from Transformers(BERT)based models for multi-class cyberbullying detection.Our approach integrates TF-IDF for lexical specificity and Word2Vec for semantic relationships,fused with BERT’s contextual embeddings to capture syntactic and semantic complexities.We evaluate the framework on a publicly available dataset of 47,000 annotated social media posts across five cyberbullying categories:age,ethnicity,gender,religion,and indirect aggression.Among BERT variants tested,BERT Base Un-Cased achieved the highest performance with 93%accuracy(standard deviation across±1%5-fold cross-validation)and an average AUC of 0.96,outperforming standalone TF-IDF(78%)and Word2Vec(82%)models.Notably,it achieved near-perfect AUC scores(0.99)for age and ethnicity-based bullying.A comparative analysis with state-of-the-art benchmarks,including Generative Pre-trained Transformer 2(GPT-2)and Text-to-Text Transfer Transformer(T5)models highlights BERT’s superiority in handling ambiguous language.This work advances cyberbullying detection by demonstrating how hybrid feature extraction and transformer models improve multi-class classification,offering a scalable solution for moderating nuanced harmful content.
基金supported by the National Natural Science Foundation of China(Grant Nos.:92477103,22273023,12474285 and 22373116)the National Key R&D Program of China(Grant No.:2019YFA0905200)+5 种基金Shanghai Municipal Natural Science Foundation(Grant No.:23ZR1418200)Natural Science Foundation of Chongqing,China(Grant No.:CSTB2023NSCQ-MSX0616)Shanghai Frontiers Science Center of Molecule Intelligent SynthesesShanghai Future Discipline Program(Quantum Science and Tech-nology)Shanghai Municipal Education Commission’s“Artificial Intelligence-Driven Research Paradigm Reform and Discipline Advancement Program”the Fundamental Research Funds for the Central Universities.
文摘The identification and optimization of mutations in nanobodies are crucial for enhancing their thera-peutic potential in disease prevention and control.However,this process is often complex and time-consuming,which limit its widespread application in practice.In this study,we developed a work-flow,named Evolutionary-Nanobody(EvoNB),to predict key mutation sites of nanobodies by combining protein language models(PLMs)and molecular dynamic(MD)simulations.By fine-tuning the ESM2 model on a large-scale nanobody dataset,the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced.The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies.Additionally,we selected four widely representative nanobodyeantigen complexes to verify the predicted effects of mutations.MD simulations analyzed the energy changes caused by these mu-tations to predict their impact on binding affinity to the targets.The results showed that multiple mu-tations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target,further validating the potential of this workflow for designing and optimizing nanobody mutations.Additionally,sequence-based predictions are generally less dependent on structural absence,allowing them to be more easily integrated with tools for structural predictions,such as AlphaFold 3.Through mutation prediction and systematic analysis of key sites,we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes.The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.
基金supported by the National Key R&D Program of China(No.2023YFC3006702)the Natural Science Foundation of Beijing Municipality(IS23117).
文摘Characterized by special morphologic,geographic,hydrologic,and societal behaviors,the water resources management of the Mediterranean catchment often shows a higher level of complexity including security issues of water supply,inundation risks,and environment management under the perspective of climate change.To have a comprehensive understanding of the Mediterranean water-cycle system,a deterministic distributed hydrologic modeling approach has been developed and presented in this study based on an application in the Var catchment(2800 km^(2))located at the French Mediterranean region.A 1D and 2D coupled model of MIKE SHE and MIKE 11 has been set up under a series of hypotheses to represent the whole hydrologic and hydrodynamic processes including rainfall-runoff,snow-melting,channel flow,overland flow,and the water exchange between land surface and unsaturated/saturated zones.The developed model was first calibrated with 4 years daily records from 2008 to 2011,then to be validated and further run within hourly time interval to produce detailed representation of the catchment water-cycle from 2012 to 2014.The deterministic distributed modeling approach presented in this study is able to represent its complicated water-cycle and used for supporting the decision‐making process of the water resources management of the catchment.
基金supported by the National Natural Science Foundation of China(Grant Nos.12020101005,12475202,12347131,and 12405289).
文摘Radio frequency capacitively coupled plasmas(RF CCPs)operated in Ar/O_(2)gas mixtures which are widely adopted in microelectronics,display,and photovoltaic industry,are investigated based on an equivalent circuit model coupled with a global model.This study focuses on the effects of singlet metastable molecule O_(2)(b^(1)∑_(8)^(+)),highly excited Herzberg states O_(2)(A^(3)∑_(u)^(+),A^(3)△_(u),c^(1)∑_(u)^(-)),and the negative ion O_(2)^(-),which are usually neglected in simulation studies.Specifically,their impact on particle densities,electronegativity,electron temperature,voltage drop across the sheath,and absorbed power in the discharge is analyzed.The results indicate that O_(2)(b^(1)∑_(8)^(+))and O_(2)^(-)exhibit relatively high densities in argon-oxygen discharges.While O_(2)(A^(3)∑_(u)^(+),A^(3)△_(u),c^(1)∑_(u)^(-))play a critical role in O_(2)b1S+g production,especially at higher pressure.The inclusion of these particles reduces the electronegativity,electron temperature,and key species densities,especially the O^(-)and O^(*)densities.Moreover,the sheath voltage drop,as well as the inductance and resistance of the plasma bulk are enhanced,while the sheath dissipation power and total absorbed power decrease slightly.With the increasing pressure,the influence of these particles on the discharge properties becomes more significant.The study also explores the generation and loss of main neutral species and charged particles within the pressure range of 20 mTorr-100 mTorr(1 Torr=1.33322×10^(2)Pa),offering insights into essential and non-essential reactions for future low-pressure O_(2)and Ar/O_(2)CCP discharge modeling.
基金National Natural Science Foundation of China(No.61601112)。
文摘The objective of this work is to develop an innovative system(ROSGPT)that merges large language models(LLMs)with the robot operating system(ROS),facilitating natural language voice control of mobile robots.This integration aims to bridge the gap between human-robot interaction(HRI)and artificial intelligence(AI).ROSGPT integrates several subsystems,including speech recognition,prompt engineering,LLM and ROS,enabling seamless control of robots through human voice or text commands.The LLM component is optimized,with its performance refined from the open-source Llama2 model through fine-tuning and quantization procedures.Through extensive experiments conducted in both real-world and virtual environments,ROSGPT demonstrates its efficacy in meeting user requirements and delivering user-friendly interactive experiences.The system demonstrates versatility and adaptability through its ability to comprehend diverse user commands and execute corresponding tasks with precision and reliability,thereby showcasing its potential for various practical applications in robotics and AI.The demonstration video can be viewed at https://iklxo6z9yv.feishu.cn/docx/Lux3dmTDxoZ5YnxWJTZcxUCWnTh.
基金funded by grants from the National Key Research and Development Program of China(Grant Nos.:2022YFE0205600 and 2022YFC3400504)the National Natural Science Foundation of China(Grant Nos.:82373792 and 82273857)the Fundamental Research Funds for the Central Universities,China,and the East China Normal University Medicine and Health Joint Fund,China(Grant No.:2022JKXYD07001).
文摘Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC’s generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.
基金financial support from the National Key Research and Development Program of China(2021YFB 3501501)the National Natural Science Foundation of China(No.22225803,22038001,22108007 and 22278011)+1 种基金Beijing Natural Science Foundation(No.Z230023)Beijing Science and Technology Commission(No.Z211100004321001).
文摘The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:CIFMS,2021-I2M-1-024The Joint Fund for the Department of Science and Technology of Yunnan Province-Kunming Medical University,Grant/Award Number:202201AY070001-007+1 种基金Open Research Fund Project of Yunnan Provincial Key Laboratory of Pharmacology of Natural Medicines,Grant/Award Number:YKLPNP-G2403The Science and Technology Leading Talent Program of Yunnan Province,Grant/Award Number:202405AB350002。
文摘Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.
基金National Science and Technology Infrastructure of China,Grant/Award Number:National Pathogen Resource Center-NPRC-32National Key Research and Development Program of China,Grant/Award Number:2023YFF0724800CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035。
文摘Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.
