BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.展开更多
Background:Scientific animal models are indispensable for studying trauma repair.This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma nu...Background:Scientific animal models are indispensable for studying trauma repair.This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma numbers,locations,and trauma attachment tension unloaders and rat age.Methods:A four-trauma self-upper,lower,left and right control model;a two-trauma self-trauma bare and ring control model;and a young and old rat trauma model were created to evaluate the condition of these traumas.Results:In the four-trauma self-control model,the healing status of the upper proximal cephalic trauma was better than that of the lower proximal caudal trauma,whereas there was no significant difference between the left and right trauma.The healing rate and postwound condition of the trauma with a ring control in the two-trauma model were better than those of the bare side.The healing speed of the old rats was slower,and the amount of extracellular matrix in the subcutaneous tissue after healing was significantly lower than that of the young rats.Conclusion:The double trauma with a ring is a more scientific and reasonable experimental model.There is a significant difference between young and old rats in the wound healing process.Therefore,the appropriate age of the rats should be selected according to the main age range of the patients with similar conditions in the clinical setting being mimicked.展开更多
Modeling HIV/AIDS progression is critical for understanding disease dynamics and improving patient care. This study compares the Exponential and Weibull survival models, focusing on their ability to capture state-spec...Modeling HIV/AIDS progression is critical for understanding disease dynamics and improving patient care. This study compares the Exponential and Weibull survival models, focusing on their ability to capture state-specific failure rates in HIV/AIDS progression. While the Exponential model offers simplicity with a constant hazard rate, it often fails to accommodate the complexities of dynamic disease progression. In contrast, the Weibull model provides flexibility by allowing hazard rates to vary over time. Both models are evaluated within the frameworks of the Cox Proportional Hazards (Cox PH) and Accelerated Failure Time (AFT) models, incorporating critical covariates such as age, gender, CD4 count, and ART status. Statistical evaluation metrics, including Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), log-likelihood, and Pseudo-R2, were employed to assess model performance across diverse patient subgroups. Results indicate that the Weibull model consistently outperforms the Exponential model in dynamic scenarios, such as younger patients and those with co-infections, while maintaining robustness in stable contexts. This study highlights the trade-off between flexibility and simplicity in survival modeling, advocating for tailored model selection to balance interpretability and predictive accuracy. These findings provide valuable insights for optimizing HIV/AIDS management strategies and advancing survival analysis methodologies.展开更多
This paper studies the global existence and large-time behaviors of weak solutions to the kinetic particle model coupled with the incompressible Navier-Stokes equations in IR3.First,we obtain the global weak solution ...This paper studies the global existence and large-time behaviors of weak solutions to the kinetic particle model coupled with the incompressible Navier-Stokes equations in IR3.First,we obtain the global weak solution using the characteristic and energy methods.Then,under the small assumption of the mass of the particle,we show that the solutions decay at the algebraic time-decay rate.Finally,it is also proved that the above rate is optimal.It should be remarked that if the particle in the coupled system vanishes(i.e.f=O),our works coincide with the classical results by Schonbek[32](J Amer Math Soc,1991,4:423-449),which can be regarded as a generalization from a single fuid model to the two-phase fluid one.展开更多
In the event of nuclear accidents and incidents,when emergency resources are scarce,rapid and high-throughput biodosimeters for massive population triage and estimation are essential to guide medical treatment.Lymphoc...In the event of nuclear accidents and incidents,when emergency resources are scarce,rapid and high-throughput biodosimeters for massive population triage and estimation are essential to guide medical treatment.Lymphocyte dynamics,chromosome aberration analysis,and micronucleus assays are mainly used to estimate the biological dose of radiation[1].However,these technologies require highly trained personnel to perform and interpret and have the limitations of time consumption and low throughput,underscoring the urgent need for the development of radiation biomarkers and early classification.Dose and temporal responses as well as efficient triage models are important facets of radiation biodosimeters.展开更多
AIM： To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats. METHODS： Immune-induced and CCL4-induced liver fi...AIM： To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats. METHODS： Immune-induced and CCL4-induced liver fibrosis models were established by dexamethasone （0.01 mg） and CCL4 respectively. Serum TIMP-1 level was detected with ELISA, while histopathological grade of liver biopsy was evaluated. Spearman rankcorrelation test was used to analyse the difference of the correlation between the TIMP-1 expression and hepatic fibrosis in the two fibrosis models. Furthermore,in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models. RESULTS： Positive correlation existed between serum TIMP-1 level of immune induced group and the histopathological stages of fibrosis liver of corresponding rats （Spearman rank-correlation test, rs = 0.812, P 0.05）, and the positive in situ hybridization signal of TIMP-1 mRNA was strong. In CCL4-induced liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant（Spearman rank-correlation test, rs = 0.229, P 〉 0.05）. And compared with immune-induced model, the positivein situ hybridization signal of TIMP-1 mRNA was weaker, while the expression variation was higher in hepatic fibrosis of the same severity. CONCLUSION： The correlations between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models are different. In immune-induced model, serum TIMP-1 level could reflect the severity of liver fibrosis, while in CCL4-induced model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and i...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.展开更多
This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experi...This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models.This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia.Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar.Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction,effective monitoring of blood glucose levels,and maintaining a high survival rate throughout the required experimental duration.展开更多
Background:Liver diseases are a major contributor to both morbidity and mortality.Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal.The use of floxed ra...Background:Liver diseases are a major contributor to both morbidity and mortality.Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal.The use of floxed rat resource has rapidly increased,but the liver-specific Cre rat lines for studying liver diseases and interested genes are limited,especially in a spatially and temporally restricted manner.Methods:RNA sequencing and real-time polymerase chain reaction(PCR)were used to screen and confirm the presence of liver-specific genes.Apoa4-Cre rats and Cyp2c11-Cre rats were produced by CRISPR/Cas9 knockin.Rosa26-imCherry rats were employed to hybridize with the Cre rats to obtain the Apoa4-Cre/Rosa26-imCherry and Cyp2c11-Cre/Rosa26-imCherry rats.The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tis-sue sections.Hematoxylin-eosin stain was used to evaluate the liver histopathologic changes.The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.Results:Apoa4 and Cyp2c11 were identified as two liver-specific genes.Apoa4-Cre and Cyp2c11-Cre rats were produced and hybridized with Rosa26-imCherry rats.The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats.All the blood biochemical parameters except low-density lipoprotein(LDL)did not change signifi-cantly in the Cre rats.No histological alterations were detected in the livers of the Cre rats.Conclusions:Liver-specific Apoa4-Cre and Cyp2c11-Cre rats have been established successfully and could be used to study gene knockout,specifically in juvenile and adult liver.展开更多
Although Steen's solution plays a crucial role in maintaining vascular oncotic pressure and reducing pulmonary edema due to its high concentration of human serum albumin during ex vivo lung perfusion(EVLP),it incu...Although Steen's solution plays a crucial role in maintaining vascular oncotic pressure and reducing pulmonary edema due to its high concentration of human serum albumin during ex vivo lung perfusion(EVLP),it incurs high costs and potential immune responses in rat models.In our preliminary research,donor lungs perfused with Steen's solution exhibited significant lung injury post transplantation,likely due to a strong immune response elicited by the high concentration of xenogenic proteins upon reperfusion.This study explores a low-cost and efficient perfusate composition for use in rat EVLP and lung transplant models.The modified perfusate employed in this study uses artificial colloids as the primary component,with an albumin concentration of only 2%,demonstrating comparable physiological parameters,metabolic levels,and pathological changes to those of Steen's solution during EVLP.Moreover,the modified composition exhibited good biocompatibility in transplantation,with minimal lung injury.In summary,the proposed perfusate offers a safer and more economical alternative for establishing rat EVLP and lung transplant models,facilitating the advancement of related research.展开更多
Consider two dependent renewal risk models with constant interest rate. By using some methods in the risk theory, uniform asymptotics for finite-time ruin probability is derived in a non-compound risk model, where cla...Consider two dependent renewal risk models with constant interest rate. By using some methods in the risk theory, uniform asymptotics for finite-time ruin probability is derived in a non-compound risk model, where claim sizes are upper tail asymptotically independent random variables with dominatedly varying tails, claim inter-arrival times follow the widely lower orthant dependent structure, and the total amount of premiums is a nonnegative stochastic process. Based on the obtained result, using the method of analysis for the tail probability of random sums, a similar result in a more complex and reasonable compound risk model is also obtained, where individual claim sizes are specialized to be extended negatively dependent and accident inter-arrival times are still widely lower orthant dependent, and both the claim sizes and the claim number have dominatedly varying tails.展开更多
Melanins are widely used in medicine, pharmacology and cosmetics. Different technologies have been used to obtain melanin including： chemical synthesis based on oxidation of tyrosine and its derivatives; extraction f...Melanins are widely used in medicine, pharmacology and cosmetics. Different technologies have been used to obtain melanin including： chemical synthesis based on oxidation of tyrosine and its derivatives; extraction from animal materials; alkaline extraction from plant material; and microbiological synthesis. A few number of works have been published that were focused on purification of water insoluble 3,4-dihy- droxy-phenylalanine-melanins （Kukulianskaia et al., 2002）. The majority of synthetic and natural melanins are insoluble in wa- ter that significantly complicates preparation of pharmacolog- ical and cosmetic preparations. Obtaining of low-cost soluble biotechnological melanin can speed up application of melanin in medicine and other fields. For the first time, melanin-syn-thesizing strain with high level of pigment synthesis - Bacillus thuringiensis was obtained. The ecologically safe technology of biosynthesis, isolation and purification of the bacterial melanin has been elaborated.展开更多
BACKGROUND： Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf （GSL） can improve function...BACKGROUND： Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf （GSL） can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease （AD）. OBJECTIVE ： To observe the effects of GSL combining with choline on learning and memory of AD model rats DESIGN ： Randomized grouping design and controlled animal study SETIING ： Department of Pharmacology, Taishan Medical College MATERIALS ： The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications： GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [（55±1）%, CV= 2%, n = 5]. Choline was provided by the Third Shanghai Laboratory Factory. METHODS ： 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline （20 mL/kg）, and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled water once in each morning for the same days. （1） Passive avoidance step-down test： Five minutes later, rats jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. （2） Morris water-maze spatial localization task： Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3 successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The training times were increased to 30 for unlearned rats. （3） Measurement of activity of choline acetylase in cerebral cortex： Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choline acetylase with radiochemistry technique. （4） Synergistic effect： It was expressed as Q value： Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = （EA＋EB-EA·EB）, EA and EB were single timing effect, respectively in GSL group and choline group. E（step-down test and Morris water maze test） = （x in model group - factual value in medicine groups）/x in model group; E （activity of choline acetylase） = （factual value in medicine groups -xin model group）/xin model group. MAIN OUTCOME MEASURES ： （1） Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; （2） activity of choline acetylase. RESULTS ： All 40 rats were involved in the final analysis. （1） Passive avoidance response： At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [（5.88±1.46）, （2.25±0.87） times; （2.63±1.06）, （0.50±0.53） times; P 〈 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase： （1.12±0.83）, （5.88±1.46） times; retesting phase： （0.38±0.74）, （2.63±1.06）times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. Spatial localization task： Training times were more in model group than sham operation group, and there was significant difference [（2.9±2.5）, （12.6±3.5） times; P 〈 0.01]. Training times were less in combination group than model group, and there was significant difference [（11.8±2.4）, （27.9±2.5） times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. （3） Activity of choline acetylase： Activity was lower in model group than sham operation group, and there was significant difference [（30.56±8.33）, （61.11 ±8.33） nkat/g; P 〈 0.01]. Activity was higher in combination group than model group and there was significant difference [（50.00±8.33）, （30.56±8.33） nkat/g, P 〈 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect. CONCLUSZON： GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.展开更多
Dopamine （DA） is one of the brain＇s fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiologic...Dopamine （DA） is one of the brain＇s fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiological functions and in the pathogenesis of important psychiatric diseases such as schizophrenia, attention-deficit/hyperactivity disorder （ADHD）, Parkinson＇s disease （PD） and others.展开更多
BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at diffe...BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at different sites. OBJECTIVE： To compare the features of animal models of complex partial epilepsy established through unilateral, bilateral and alternate-side kindling at hippocampus and successful rate of modeling among these 3 different ways. DESIGN： A randomized and controlled animal experiment SETTING： Department of Neurology, Qilu Hospital, Shandong University MATERIALS： Totally 60 healthy adult Wistar rats, weighing 200 to 300 g, of either gender, were used in this experiment. BL-410 biological functional experimental system （Taimeng Science and Technology Co. Ltd, Chengdu） and SE-7102 type electronic stimulator （Guangdian Company, Japan） were used in the experiment. METHODS： This experiment was carried out in the Experimental Animal Center of Shandong University from April to June 2004. After rats were anesthetized, electrode was implanted into the hippocampus. From the first day of measurement of afterdischarge threshold value, rats were given two-square-wave suprathreshold stimulation once per day with 400 μA intensity, 1ms wave length, 60 Hz frequency for 1 s duration. Left hippocampus was stimulated in unilateral kindling group, bilateral hippocampi were stimulated in bilateral kindling group, and left and right hippocampi were stimulated alternately every day in the alternate-side kindling group. Seizure intensity was scored： grade 0： normal, 1： wet dog-like shivering, facial spasm, such as, winking, touching the beard, rhythmic chewing and so on; 2： rhythmic nodding; 3： forelimb spasm;4： standing accompanied by bilateral forelimb spasm;5： tumbling, losing balance, four limbs spasm. Modeling was successful when seizure intensity reached grade 5. t test was used for the comparison of mean value between two samples. MAIN OUTCOME MEASURES： Comparison of the successful rate of modeling, the times of stimulation to reach intensity of grade 5, the lasting time of seizure of grade 3 of rats in each group. RESULTS： Four rats of alternate-side kindling group dropped out due to infection-induced electrode loss, and 56 rats were involved in the result analysis. The successful rate of unilateral kindling group, bilateral kin- dling group and alternate-side kindling group was 55%（11/20）,100%（16/16）and 100%（20/20）, respective- ly. The stimuli to reach the grade 5 spasm were significantly more in the bilateral kindling group than in the unilateral kindling group [（30.63±3.48）, （19.36±3.47）times, t=8.268, P 〈 0.01], and those were significantly fewer in the alternate-side kindling group than in the unilateral kindling group [（ 10.85±1.98）times, t=-8.744, P 〈 0.01]. The duration of grade 3 spasm was significantly longer in the bilateral kindling group than in the unilateral kindling group [（9.75±2.59）, （3.21 ±1.58）days,t=-8.183,P 〈 0.01], Among 20 successful rats of al- ternate-side kindling group, grade 5 spasm was found in the left hippocampi of 11 rats, but grade 3 spasm in their right hippocampi; Grade 5 spasm was found in the right hippocampi of the other 9 rats, grade 4 spasm in the left hippocampus of 1 rat and grade 3 of 8 rats. CONCLUSION ： The speed of establishing epilepsy seizure model by alternate-side kindling is faster than that by unilateral kindling, while that by bilateral kindling is slower than that by unilateral kindling. The successful rate is very high to establish complex partial epilepsy with alternate-side or bilateral kindling. Epilepsy seizure established by alternate-side kindling has antagonistic effect of kindling and the seizure duration of grade 3 spasm is prolonged.展开更多
This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to use...This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to user behavior and platform-driven moderation on social media.The proposed methodological framework(1)utilizes large language models for social media post analysis and categorization,(2)employs k-means clustering for content characterization,and(3)incorporates the TODIM(Tomada de Decisão Interativa Multicritério)method to determine moderation strategies based on expert judgments.In general,the fully integrated framework leverages the strengths of these intelligent systems in a more systematic evaluation of large-scale decision problems.When applied in social media moderation,this approach promotes nuanced and context-sensitive self-moderation by taking into account factors such as cultural background and geographic location.The application of this framework is demonstrated within Facebook groups.Eight distinct content clusters encompassing safety,harassment,diversity,and misinformation are identified.Analysis revealed a preference for content removal across all clusters,suggesting a cautious approach towards potentially harmful content.However,the framework also highlights the use of other moderation actions,like account suspension,depending on the content category.These findings contribute to the growing body of research on self-moderation and offer valuable insights for creating safer and more inclusive online spaces within smaller communities.展开更多
It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To b...It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.展开更多
Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted th...Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted therapy;however,their clinical benefits are limited.Therefore,developing new models to evaluate the therapeutic potential of novel molecules is essential.Fingolimod and Dimethyl Fumarate(DMF),currently used to treat multiple sclerosis,have recently been shown to have anti-cancer effects in several preclinical tumor models.This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.Methods:In this study,we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo,which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.Results:In vitro,both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines.Additionally,Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.Conclusions:Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib,these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer.However,further work is still necessary to fully characterize how these drugs affect tumor progression.展开更多
Large language models(LLMs)have revolutionized AI applications across diverse domains.However,their widespread deployment has introduced critical security vulnerabilities,particularly prompt injection attacks that man...Large language models(LLMs)have revolutionized AI applications across diverse domains.However,their widespread deployment has introduced critical security vulnerabilities,particularly prompt injection attacks that manipulate model behavior through malicious instructions.Following Kitchenham’s guidelines,this systematic review synthesizes 128 peer-reviewed studies from 2022 to 2025 to provide a unified understanding of this rapidly evolving threat landscape.Our findings reveal a swift progression from simple direct injections to sophisticated multimodal attacks,achieving over 90%success rates against unprotected systems.In response,defense mechanisms show varying effectiveness:input preprocessing achieves 60%–80%detection rates and advanced architectural defenses demonstrate up to 95%protection against known patterns,though significant gaps persist against novel attack vectors.We identified 37 distinct defense approaches across three categories,but standardized evaluation frameworks remain limited.Our analysis attributes these vulnerabilities to fundamental LLM architectural limitations,such as the inability to distinguish instructions from data and attention mechanism vulnerabilities.This highlights critical research directions such as formal verification methods,standardized evaluation protocols,and architectural innovations for inherently secure LLM designs.展开更多
Online Public Opinion Reports consolidate news and social media for timely crisis management by governments and enterprises.While large language models(LLMs)enable automated report generation,this specific domain lack...Online Public Opinion Reports consolidate news and social media for timely crisis management by governments and enterprises.While large language models(LLMs)enable automated report generation,this specific domain lacks formal task definitions and corresponding benchmarks.To bridge this gap,we define the Automated Online Public Opinion Report Generation(OPOR-Gen)task and construct OPOR-Bench,an event-centric dataset with 463 crisis events across 108 countries(comprising 8.8 K news articles and 185 K tweets).To evaluate report quality,we propose OPOR-Eval,a novel agent-based framework that simulates human expert evaluation.Validation experiments show OPOR-Eval achieves a high Spearman’s correlation(ρ=0.70)with human judgments,though challenges in temporal reasoning persist.This work establishes an initial foundation for advancing automated public opinion reporting research.展开更多
基金Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
基金Shandong Provincial Natural Science Foundation,Grant/Award Number:ZR2022MH211the Key Program of Shandong Provincial Natural Science Foundation,Grant/Award Number:ZR2020KE018National Natural Science Foundation of China,Grant/Award Number:52003068。
文摘Background:Scientific animal models are indispensable for studying trauma repair.This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma numbers,locations,and trauma attachment tension unloaders and rat age.Methods:A four-trauma self-upper,lower,left and right control model;a two-trauma self-trauma bare and ring control model;and a young and old rat trauma model were created to evaluate the condition of these traumas.Results:In the four-trauma self-control model,the healing status of the upper proximal cephalic trauma was better than that of the lower proximal caudal trauma,whereas there was no significant difference between the left and right trauma.The healing rate and postwound condition of the trauma with a ring control in the two-trauma model were better than those of the bare side.The healing speed of the old rats was slower,and the amount of extracellular matrix in the subcutaneous tissue after healing was significantly lower than that of the young rats.Conclusion:The double trauma with a ring is a more scientific and reasonable experimental model.There is a significant difference between young and old rats in the wound healing process.Therefore,the appropriate age of the rats should be selected according to the main age range of the patients with similar conditions in the clinical setting being mimicked.
文摘Modeling HIV/AIDS progression is critical for understanding disease dynamics and improving patient care. This study compares the Exponential and Weibull survival models, focusing on their ability to capture state-specific failure rates in HIV/AIDS progression. While the Exponential model offers simplicity with a constant hazard rate, it often fails to accommodate the complexities of dynamic disease progression. In contrast, the Weibull model provides flexibility by allowing hazard rates to vary over time. Both models are evaluated within the frameworks of the Cox Proportional Hazards (Cox PH) and Accelerated Failure Time (AFT) models, incorporating critical covariates such as age, gender, CD4 count, and ART status. Statistical evaluation metrics, including Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), log-likelihood, and Pseudo-R2, were employed to assess model performance across diverse patient subgroups. Results indicate that the Weibull model consistently outperforms the Exponential model in dynamic scenarios, such as younger patients and those with co-infections, while maintaining robustness in stable contexts. This study highlights the trade-off between flexibility and simplicity in survival modeling, advocating for tailored model selection to balance interpretability and predictive accuracy. These findings provide valuable insights for optimizing HIV/AIDS management strategies and advancing survival analysis methodologies.
基金supported by the Anhui Provincial Natural Science Foundation(2408085QA031)the third author's work was supported by the National Natural Science Foundation of China(12001033).
文摘This paper studies the global existence and large-time behaviors of weak solutions to the kinetic particle model coupled with the incompressible Navier-Stokes equations in IR3.First,we obtain the global weak solution using the characteristic and energy methods.Then,under the small assumption of the mass of the particle,we show that the solutions decay at the algebraic time-decay rate.Finally,it is also proved that the above rate is optimal.It should be remarked that if the particle in the coupled system vanishes(i.e.f=O),our works coincide with the classical results by Schonbek[32](J Amer Math Soc,1991,4:423-449),which can be regarded as a generalization from a single fuid model to the two-phase fluid one.
基金supported by the National Natural Science Foundation of China(No.82173463)the Young Scholar Science Foundation of China CDC(No.2023A204)the NIRP Research Fund for Young Scholars(No.2024NB01).
文摘In the event of nuclear accidents and incidents,when emergency resources are scarce,rapid and high-throughput biodosimeters for massive population triage and estimation are essential to guide medical treatment.Lymphocyte dynamics,chromosome aberration analysis,and micronucleus assays are mainly used to estimate the biological dose of radiation[1].However,these technologies require highly trained personnel to perform and interpret and have the limitations of time consumption and low throughput,underscoring the urgent need for the development of radiation biomarkers and early classification.Dose and temporal responses as well as efficient triage models are important facets of radiation biodosimeters.
基金Supported by the Postdoctoral Science Foundation of China, No.1999-10the Science and Technology Foundation of Shaanxi Province, China, No. 2003K10G63
文摘AIM： To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats. METHODS： Immune-induced and CCL4-induced liver fibrosis models were established by dexamethasone （0.01 mg） and CCL4 respectively. Serum TIMP-1 level was detected with ELISA, while histopathological grade of liver biopsy was evaluated. Spearman rankcorrelation test was used to analyse the difference of the correlation between the TIMP-1 expression and hepatic fibrosis in the two fibrosis models. Furthermore,in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models. RESULTS： Positive correlation existed between serum TIMP-1 level of immune induced group and the histopathological stages of fibrosis liver of corresponding rats （Spearman rank-correlation test, rs = 0.812, P 0.05）, and the positive in situ hybridization signal of TIMP-1 mRNA was strong. In CCL4-induced liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant（Spearman rank-correlation test, rs = 0.229, P 〉 0.05）. And compared with immune-induced model, the positivein situ hybridization signal of TIMP-1 mRNA was weaker, while the expression variation was higher in hepatic fibrosis of the same severity. CONCLUSION： The correlations between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models are different. In immune-induced model, serum TIMP-1 level could reflect the severity of liver fibrosis, while in CCL4-induced model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.
基金Correspondence:Christina Gertrude Yap,Jeffrey Cheah School of Medicine and Health Sciences,Monash University,Jalan Lagoon Selatan,Bandar Sunway,Subang Jaya 47500,Selangor,Malaysia.Email:christina.yap@monash.edu。
文摘This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models.This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia.Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar.Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction,effective monitoring of blood glucose levels,and maintaining a high survival rate throughout the required experimental duration.
基金CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2021-I2M-1-035National Natural Science Foundation of China,Grant/Award Number:31970508。
文摘Background:Liver diseases are a major contributor to both morbidity and mortality.Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal.The use of floxed rat resource has rapidly increased,but the liver-specific Cre rat lines for studying liver diseases and interested genes are limited,especially in a spatially and temporally restricted manner.Methods:RNA sequencing and real-time polymerase chain reaction(PCR)were used to screen and confirm the presence of liver-specific genes.Apoa4-Cre rats and Cyp2c11-Cre rats were produced by CRISPR/Cas9 knockin.Rosa26-imCherry rats were employed to hybridize with the Cre rats to obtain the Apoa4-Cre/Rosa26-imCherry and Cyp2c11-Cre/Rosa26-imCherry rats.The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tis-sue sections.Hematoxylin-eosin stain was used to evaluate the liver histopathologic changes.The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.Results:Apoa4 and Cyp2c11 were identified as two liver-specific genes.Apoa4-Cre and Cyp2c11-Cre rats were produced and hybridized with Rosa26-imCherry rats.The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats.All the blood biochemical parameters except low-density lipoprotein(LDL)did not change signifi-cantly in the Cre rats.No histological alterations were detected in the livers of the Cre rats.Conclusions:Liver-specific Apoa4-Cre and Cyp2c11-Cre rats have been established successfully and could be used to study gene knockout,specifically in juvenile and adult liver.
文摘Although Steen's solution plays a crucial role in maintaining vascular oncotic pressure and reducing pulmonary edema due to its high concentration of human serum albumin during ex vivo lung perfusion(EVLP),it incurs high costs and potential immune responses in rat models.In our preliminary research,donor lungs perfused with Steen's solution exhibited significant lung injury post transplantation,likely due to a strong immune response elicited by the high concentration of xenogenic proteins upon reperfusion.This study explores a low-cost and efficient perfusate composition for use in rat EVLP and lung transplant models.The modified perfusate employed in this study uses artificial colloids as the primary component,with an albumin concentration of only 2%,demonstrating comparable physiological parameters,metabolic levels,and pathological changes to those of Steen's solution during EVLP.Moreover,the modified composition exhibited good biocompatibility in transplantation,with minimal lung injury.In summary,the proposed perfusate offers a safer and more economical alternative for establishing rat EVLP and lung transplant models,facilitating the advancement of related research.
基金The National Natural Science Foundation of China(No.11001052,11171065,71171046)China Postdoctoral Science Foundation(No.2012M520964)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20131339)the Qing Lan Project of Jiangsu Province
文摘Consider two dependent renewal risk models with constant interest rate. By using some methods in the risk theory, uniform asymptotics for finite-time ruin probability is derived in a non-compound risk model, where claim sizes are upper tail asymptotically independent random variables with dominatedly varying tails, claim inter-arrival times follow the widely lower orthant dependent structure, and the total amount of premiums is a nonnegative stochastic process. Based on the obtained result, using the method of analysis for the tail probability of random sums, a similar result in a more complex and reasonable compound risk model is also obtained, where individual claim sizes are specialized to be extended negatively dependent and accident inter-arrival times are still widely lower orthant dependent, and both the claim sizes and the claim number have dominatedly varying tails.
文摘Melanins are widely used in medicine, pharmacology and cosmetics. Different technologies have been used to obtain melanin including： chemical synthesis based on oxidation of tyrosine and its derivatives; extraction from animal materials; alkaline extraction from plant material; and microbiological synthesis. A few number of works have been published that were focused on purification of water insoluble 3,4-dihy- droxy-phenylalanine-melanins （Kukulianskaia et al., 2002）. The majority of synthetic and natural melanins are insoluble in wa- ter that significantly complicates preparation of pharmacolog- ical and cosmetic preparations. Obtaining of low-cost soluble biotechnological melanin can speed up application of melanin in medicine and other fields. For the first time, melanin-syn-thesizing strain with high level of pigment synthesis - Bacillus thuringiensis was obtained. The ecologically safe technology of biosynthesis, isolation and purification of the bacterial melanin has been elaborated.
文摘BACKGROUND： Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf （GSL） can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease （AD）. OBJECTIVE ： To observe the effects of GSL combining with choline on learning and memory of AD model rats DESIGN ： Randomized grouping design and controlled animal study SETIING ： Department of Pharmacology, Taishan Medical College MATERIALS ： The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications： GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [（55±1）%, CV= 2%, n = 5]. Choline was provided by the Third Shanghai Laboratory Factory. METHODS ： 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline （20 mL/kg）, and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled water once in each morning for the same days. （1） Passive avoidance step-down test： Five minutes later, rats jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. （2） Morris water-maze spatial localization task： Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3 successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The training times were increased to 30 for unlearned rats. （3） Measurement of activity of choline acetylase in cerebral cortex： Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choline acetylase with radiochemistry technique. （4） Synergistic effect： It was expressed as Q value： Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = （EA＋EB-EA·EB）, EA and EB were single timing effect, respectively in GSL group and choline group. E（step-down test and Morris water maze test） = （x in model group - factual value in medicine groups）/x in model group; E （activity of choline acetylase） = （factual value in medicine groups -xin model group）/xin model group. MAIN OUTCOME MEASURES ： （1） Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; （2） activity of choline acetylase. RESULTS ： All 40 rats were involved in the final analysis. （1） Passive avoidance response： At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [（5.88±1.46）, （2.25±0.87） times; （2.63±1.06）, （0.50±0.53） times; P 〈 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase： （1.12±0.83）, （5.88±1.46） times; retesting phase： （0.38±0.74）, （2.63±1.06）times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. Spatial localization task： Training times were more in model group than sham operation group, and there was significant difference [（2.9±2.5）, （12.6±3.5） times; P 〈 0.01]. Training times were less in combination group than model group, and there was significant difference [（11.8±2.4）, （27.9±2.5） times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. （3） Activity of choline acetylase： Activity was lower in model group than sham operation group, and there was significant difference [（30.56±8.33）, （61.11 ±8.33） nkat/g; P 〈 0.01]. Activity was higher in combination group than model group and there was significant difference [（50.00±8.33）, （30.56±8.33） nkat/g, P 〈 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect. CONCLUSZON： GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.
基金supported by the Russian Science Foundation,No.17-75-20177(to IS) and No.14-50-00069(to RRG)
文摘Dopamine （DA） is one of the brain＇s fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiological functions and in the pathogenesis of important psychiatric diseases such as schizophrenia, attention-deficit/hyperactivity disorder （ADHD）, Parkinson＇s disease （PD） and others.
文摘BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at different sites. OBJECTIVE： To compare the features of animal models of complex partial epilepsy established through unilateral, bilateral and alternate-side kindling at hippocampus and successful rate of modeling among these 3 different ways. DESIGN： A randomized and controlled animal experiment SETTING： Department of Neurology, Qilu Hospital, Shandong University MATERIALS： Totally 60 healthy adult Wistar rats, weighing 200 to 300 g, of either gender, were used in this experiment. BL-410 biological functional experimental system （Taimeng Science and Technology Co. Ltd, Chengdu） and SE-7102 type electronic stimulator （Guangdian Company, Japan） were used in the experiment. METHODS： This experiment was carried out in the Experimental Animal Center of Shandong University from April to June 2004. After rats were anesthetized, electrode was implanted into the hippocampus. From the first day of measurement of afterdischarge threshold value, rats were given two-square-wave suprathreshold stimulation once per day with 400 μA intensity, 1ms wave length, 60 Hz frequency for 1 s duration. Left hippocampus was stimulated in unilateral kindling group, bilateral hippocampi were stimulated in bilateral kindling group, and left and right hippocampi were stimulated alternately every day in the alternate-side kindling group. Seizure intensity was scored： grade 0： normal, 1： wet dog-like shivering, facial spasm, such as, winking, touching the beard, rhythmic chewing and so on; 2： rhythmic nodding; 3： forelimb spasm;4： standing accompanied by bilateral forelimb spasm;5： tumbling, losing balance, four limbs spasm. Modeling was successful when seizure intensity reached grade 5. t test was used for the comparison of mean value between two samples. MAIN OUTCOME MEASURES： Comparison of the successful rate of modeling, the times of stimulation to reach intensity of grade 5, the lasting time of seizure of grade 3 of rats in each group. RESULTS： Four rats of alternate-side kindling group dropped out due to infection-induced electrode loss, and 56 rats were involved in the result analysis. The successful rate of unilateral kindling group, bilateral kin- dling group and alternate-side kindling group was 55%（11/20）,100%（16/16）and 100%（20/20）, respective- ly. The stimuli to reach the grade 5 spasm were significantly more in the bilateral kindling group than in the unilateral kindling group [（30.63±3.48）, （19.36±3.47）times, t=8.268, P 〈 0.01], and those were significantly fewer in the alternate-side kindling group than in the unilateral kindling group [（ 10.85±1.98）times, t=-8.744, P 〈 0.01]. The duration of grade 3 spasm was significantly longer in the bilateral kindling group than in the unilateral kindling group [（9.75±2.59）, （3.21 ±1.58）days,t=-8.183,P 〈 0.01], Among 20 successful rats of al- ternate-side kindling group, grade 5 spasm was found in the left hippocampi of 11 rats, but grade 3 spasm in their right hippocampi; Grade 5 spasm was found in the right hippocampi of the other 9 rats, grade 4 spasm in the left hippocampus of 1 rat and grade 3 of 8 rats. CONCLUSION ： The speed of establishing epilepsy seizure model by alternate-side kindling is faster than that by unilateral kindling, while that by bilateral kindling is slower than that by unilateral kindling. The successful rate is very high to establish complex partial epilepsy with alternate-side or bilateral kindling. Epilepsy seizure established by alternate-side kindling has antagonistic effect of kindling and the seizure duration of grade 3 spasm is prolonged.
基金funded by the Office of the Vice-President for Research and Development of Cebu Technological University.
文摘This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to user behavior and platform-driven moderation on social media.The proposed methodological framework(1)utilizes large language models for social media post analysis and categorization,(2)employs k-means clustering for content characterization,and(3)incorporates the TODIM(Tomada de Decisão Interativa Multicritério)method to determine moderation strategies based on expert judgments.In general,the fully integrated framework leverages the strengths of these intelligent systems in a more systematic evaluation of large-scale decision problems.When applied in social media moderation,this approach promotes nuanced and context-sensitive self-moderation by taking into account factors such as cultural background and geographic location.The application of this framework is demonstrated within Facebook groups.Eight distinct content clusters encompassing safety,harassment,diversity,and misinformation are identified.Analysis revealed a preference for content removal across all clusters,suggesting a cautious approach towards potentially harmful content.However,the framework also highlights the use of other moderation actions,like account suspension,depending on the content category.These findings contribute to the growing body of research on self-moderation and offer valuable insights for creating safer and more inclusive online spaces within smaller communities.
基金Supported by grants for the MICINN(PSI2009-10532)“Fundacio La Marato TV3”(ref.092630/31)and 2009SGR-0051.I.O.is recipient of a PhD FI fellowship(DGR 2014).
文摘It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.
基金supported by Porsolt SAS,https://www.porsolt.com/.
文摘Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted therapy;however,their clinical benefits are limited.Therefore,developing new models to evaluate the therapeutic potential of novel molecules is essential.Fingolimod and Dimethyl Fumarate(DMF),currently used to treat multiple sclerosis,have recently been shown to have anti-cancer effects in several preclinical tumor models.This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.Methods:In this study,we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo,which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.Results:In vitro,both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines.Additionally,Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.Conclusions:Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib,these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer.However,further work is still necessary to fully characterize how these drugs affect tumor progression.
基金supported by 2023 Higher Education Scientific Research Planning Project of China Society of Higher Education(No.23PG0408)2023 Philosophy and Social Science Research Programs in Jiangsu Province(No.2023SJSZ0993)+2 种基金Nantong Science and Technology Project(No.JC2023070)Key Project of Jiangsu Province Education Science 14th Five-Year Plan(Grant No.B-b/2024/02/41)the Open Fund of Advanced Cryptography and System Security Key Laboratory of Sichuan Province(Grant No.SKLACSS-202407).
文摘Large language models(LLMs)have revolutionized AI applications across diverse domains.However,their widespread deployment has introduced critical security vulnerabilities,particularly prompt injection attacks that manipulate model behavior through malicious instructions.Following Kitchenham’s guidelines,this systematic review synthesizes 128 peer-reviewed studies from 2022 to 2025 to provide a unified understanding of this rapidly evolving threat landscape.Our findings reveal a swift progression from simple direct injections to sophisticated multimodal attacks,achieving over 90%success rates against unprotected systems.In response,defense mechanisms show varying effectiveness:input preprocessing achieves 60%–80%detection rates and advanced architectural defenses demonstrate up to 95%protection against known patterns,though significant gaps persist against novel attack vectors.We identified 37 distinct defense approaches across three categories,but standardized evaluation frameworks remain limited.Our analysis attributes these vulnerabilities to fundamental LLM architectural limitations,such as the inability to distinguish instructions from data and attention mechanism vulnerabilities.This highlights critical research directions such as formal verification methods,standardized evaluation protocols,and architectural innovations for inherently secure LLM designs.
基金supported by the Fundamental Research Funds for the Central Universities(No.CUC25SG013)the Foundation of Key Laboratory of Education Informatization for Nationalities(Yunnan Normal University),Ministry of Education(No.EIN2024C006).
文摘Online Public Opinion Reports consolidate news and social media for timely crisis management by governments and enterprises.While large language models(LLMs)enable automated report generation,this specific domain lacks formal task definitions and corresponding benchmarks.To bridge this gap,we define the Automated Online Public Opinion Report Generation(OPOR-Gen)task and construct OPOR-Bench,an event-centric dataset with 463 crisis events across 108 countries(comprising 8.8 K news articles and 185 K tweets).To evaluate report quality,we propose OPOR-Eval,a novel agent-based framework that simulates human expert evaluation.Validation experiments show OPOR-Eval achieves a high Spearman’s correlation(ρ=0.70)with human judgments,though challenges in temporal reasoning persist.This work establishes an initial foundation for advancing automated public opinion reporting research.
