T.S.Eliot's works have the didactic purpose of turning his readers away from what he considered the selfindulgence of the Romantics and toward the sterner splendors of Elizabethan drama and the 17th-century metaph...T.S.Eliot's works have the didactic purpose of turning his readers away from what he considered the selfindulgence of the Romantics and toward the sterner splendors of Elizabethan drama and the 17th-century metaphysical poetry.Associated with the rise of literary modernism,he was established as the voice of a disillusioned generation by The Waste Land(1922).Especially,Eliot's description of the discourse of animality received highly artistic effect on the aspect of expressing his "impersonal theory".The discourse of animality in The Waste Land in plenty,thus,it made the author's expressive force more vivid.Furthermore,various imagos of different animals drew a mythical picture of modern waste land.So that,Eliot's The Waste Land also has the epic signification.展开更多
Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(...Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.展开更多
Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and e...Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.展开更多
Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.展开更多
Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The fie...Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.展开更多
CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expresse...CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.展开更多
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the i...Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.展开更多
Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and ...Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and jaundice.HEV infection may become chronic in immunosuppressed individuals.In addition,HEV infection can also cause several extrahepatic manifestations.HEV exists in a wide range of hosts in nature and can be transmitted across species.Hence,animals susceptible to HEV can be used as models.The establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis E.This review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other animals.For each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV infection.The advantages and disadvantages of these animal models were also emphasized.This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.展开更多
Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attr...Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.展开更多
Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclea...Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.展开更多
Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who ma...Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive decline.This study examines a nationally representative sample of military veterans to address this gap in knowledge.展开更多
Functionally referential signals are a complex form of communication that conveys information about the external environment.Such signals have been found in a range of mammal and bird species and have helped us unders...Functionally referential signals are a complex form of communication that conveys information about the external environment.Such signals have been found in a range of mammal and bird species and have helped us understand the complexities of animal communication.Corvids are well known for their extraordinary cognitive abilities,but relatively little attention has been paid to their vocal function.Here,we investigated the functionally referential signals of a cooperatively breeding corvid species,Azure-winged Magpie(Cyanopica cyanus).Through field observations,we suggest that Azure-winged Magpie uses referential alarm calls to distinguish two types of threats:’rasp’ calls for terrestrial threats and ’chatter’ calls for aerial threats.A playback experiment revealed that Azure-winged Magpies responded to the two call types with qualitatively different behaviors.They sought cover by flying into the bushes in response to the ’chatter’ calls,and flew to or stayed at higher positions in response to ’rasp’ calls,displaying a shorter response time to ’chatter’ calls.Significant differences in acoustic structure were found between the two types of calls.Given the extensive cognitive abilities of corvids and the fact that referential signals were once thought to be unique to primates,these findings are important for expanding our understanding of social communication and language evolution.展开更多
Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of posts...Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.展开更多
Food Science of Animal Products (ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food mate...Food Science of Animal Products (ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.展开更多
Food Science of Animal Products(ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food mater...Food Science of Animal Products(ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.The research scope includes the quality and processing characteristics of food raw materials.展开更多
BACKGROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model ...BACKGROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control.We designed a Tshaped magnet system to overcome these problems and verified its effectiveness via animal experiments.AIM To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs.METHODS Twelve beagles were randomly assigned to groups in which magnets of the Tshaped scheme(study group,n=6)or normal magnets(control group,n=6)were implanted into the trachea and esophagus separately under gastroscopy.Operation time,operation success rate,and accidental injury were recorded.After operation,the presence and timing of cough and the time of magnet shedding were observed.Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing,and gross specimens of TEFs were obtained.Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery,and gross specimens were obtained.Fistula size was measured in all animals,and then harvested fistula specimens were examined by hematoxylin and eosin(HE)and Masson trichrome staining.RESULTS The operation success rate was 100%for both groups.Operation time did not differ between the study group(5.25 min±1.29 min)and the control group(4.75 min±1.70 min;P=0.331).No bleeding,perforation,or unplanned magnet attraction occurred in any animal during the operation.In the early postoperative period,all dogs ate freely and were generally in good condition.Dogs in the control group had severe cough after drinking water at 6-9 d after surgery.X-ray indicated that the magnets had entered the stomach,and gastroscopy showed TEF formation.Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm±1.29 mm(range,3.52-6.56 mm).HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas.Dogs in the study group did not exhibit obvious coughing after surgery.X-ray examination 2 wk after surgery indicated fixed magnet positioning,and gastroscopy showed no change in magnet positioning.The magnets were removed using a snare under endoscopy,and TEF was observed.Gross specimens showed well-formed fistulas with a diameter of 6.11 mm±0.16 mm(range,5.92-6.36 mm),which exceeded that in the control group(P<0.001).Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining,and the structure was more regular than that in the control group.CONCLUSION Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets.Most importantly,this model offers better controllability,which improves the flexibility of follow-up studies.展开更多
In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases.Currently,...In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases.Currently,implantable electrochemical microsensors have emerged as a prominent area of research.These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration.They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner,characterized by their bloodless,painless features,and exceptional performance.The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts.This review commenced with a comprehensive discussion of the construction of microsensors,including the materials utilized and the methods employed for fabrication.Following this,we proceeded to explore the various implantation technologies employed for electrochemical microsensors.In addition,a comprehensive overview was provided of the various applications of implantable electrochemical microsensors,specifically in the monitoring of diseases and the investigation of disease mechanisms.Lastly,a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.展开更多
Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poo...Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.展开更多
Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it i...Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.展开更多
文摘T.S.Eliot's works have the didactic purpose of turning his readers away from what he considered the selfindulgence of the Romantics and toward the sterner splendors of Elizabethan drama and the 17th-century metaphysical poetry.Associated with the rise of literary modernism,he was established as the voice of a disillusioned generation by The Waste Land(1922).Especially,Eliot's description of the discourse of animality received highly artistic effect on the aspect of expressing his "impersonal theory".The discourse of animality in The Waste Land in plenty,thus,it made the author's expressive force more vivid.Furthermore,various imagos of different animals drew a mythical picture of modern waste land.So that,Eliot's The Waste Land also has the epic signification.
基金supported by the National Key Research and Development Program of China (2021YFF0702201)National Natural Science Foundation of China (81873736,31872779,81830032)+2 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001,2021A1515012526)Natural Science Foundation of Guangdong Province (2021A1515012526,2022A1515012651)。
文摘Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.
基金supported by the National Key Research and Development Program of China (2021YFA0805902,2022YFF0710703)National Natural Science Foundation of China (32201257)+1 种基金Science and Technology Innovation Project of Xiongan New Area (2022XAGG0121)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2019QNRC001)。
文摘Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.
基金supported by the National Natural Science Foundation of China (31970574)。
文摘Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.
基金supported by the National Major Project of Research and Development,No.2022YFA1105500(to SZ)the National Natural Science Foundation of China,No.81870975(to SZ)Innovation Program for Graduate Students in Jiangsu Province of China,No.KYCX223335(to MZ)。
文摘CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金supported by the National Natural Science Foundation of China,No.81772421(to YH).
文摘Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.
基金This study was supported by grants from the National Natural Science Foundation of China(82272396)the Fundamental Research Funds for the Central Universities(226-2022-00061).
文摘Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and jaundice.HEV infection may become chronic in immunosuppressed individuals.In addition,HEV infection can also cause several extrahepatic manifestations.HEV exists in a wide range of hosts in nature and can be transmitted across species.Hence,animals susceptible to HEV can be used as models.The establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis E.This review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other animals.For each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV infection.The advantages and disadvantages of these animal models were also emphasized.This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.
基金supported by Natural Science Foundation of Hubei Province(2021CFB401)。
文摘Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.
基金the auspices of the Royal British Legion Centre for Blast Injury Studies at Imperial College Londonthe financial support of the Royal British Legion。
文摘Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.
基金supported by the National Institutes of Health(NIA R01AG057767 and NIA R01AG061937)Dale and Deborah Smith Center for Alzheimer's Research and Treatment,Kenneth Stark Endowment.
文摘Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive decline.This study examines a nationally representative sample of military veterans to address this gap in knowledge.
基金funded by the National Natural Science Foundation of China (Grant No. 32170516, 31872243 to Y.Z.)。
文摘Functionally referential signals are a complex form of communication that conveys information about the external environment.Such signals have been found in a range of mammal and bird species and have helped us understand the complexities of animal communication.Corvids are well known for their extraordinary cognitive abilities,but relatively little attention has been paid to their vocal function.Here,we investigated the functionally referential signals of a cooperatively breeding corvid species,Azure-winged Magpie(Cyanopica cyanus).Through field observations,we suggest that Azure-winged Magpie uses referential alarm calls to distinguish two types of threats:’rasp’ calls for terrestrial threats and ’chatter’ calls for aerial threats.A playback experiment revealed that Azure-winged Magpies responded to the two call types with qualitatively different behaviors.They sought cover by flying into the bushes in response to the ’chatter’ calls,and flew to or stayed at higher positions in response to ’rasp’ calls,displaying a shorter response time to ’chatter’ calls.Significant differences in acoustic structure were found between the two types of calls.Given the extensive cognitive abilities of corvids and the fact that referential signals were once thought to be unique to primates,these findings are important for expanding our understanding of social communication and language evolution.
基金supported by the National Natural Science Foundation of China(82171506 and 31872778)Discipline Innovative Engineering Plan(111 Program)of China(B13036)+3 种基金Key Laboratory Grant from Hunan Province(2016TP1006)Department of Science and Technology of Hunan Province(2021DK2001,Innovative Team Program 2019RS1010)Innovation-Driven Team Project from Central South University(2020CX016)Hunan Hundred Talents Program for Young Outstanding Scientists。
文摘Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.
文摘Food Science of Animal Products (ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.
文摘Food Science of Animal Products(ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.The research scope includes the quality and processing characteristics of food raw materials.
基金Supported by the Key Research&Development Program of Shaanxi Province of China,No.2024SF-YBXM-447Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University,No.2022MS-07+1 种基金Fundamental Research Funds for the Central Universities,No.xzy022023068Natural Science Foundation of Shaanxi Province,No.2023-JC-QN-0814.
文摘BACKGROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control.We designed a Tshaped magnet system to overcome these problems and verified its effectiveness via animal experiments.AIM To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs.METHODS Twelve beagles were randomly assigned to groups in which magnets of the Tshaped scheme(study group,n=6)or normal magnets(control group,n=6)were implanted into the trachea and esophagus separately under gastroscopy.Operation time,operation success rate,and accidental injury were recorded.After operation,the presence and timing of cough and the time of magnet shedding were observed.Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing,and gross specimens of TEFs were obtained.Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery,and gross specimens were obtained.Fistula size was measured in all animals,and then harvested fistula specimens were examined by hematoxylin and eosin(HE)and Masson trichrome staining.RESULTS The operation success rate was 100%for both groups.Operation time did not differ between the study group(5.25 min±1.29 min)and the control group(4.75 min±1.70 min;P=0.331).No bleeding,perforation,or unplanned magnet attraction occurred in any animal during the operation.In the early postoperative period,all dogs ate freely and were generally in good condition.Dogs in the control group had severe cough after drinking water at 6-9 d after surgery.X-ray indicated that the magnets had entered the stomach,and gastroscopy showed TEF formation.Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm±1.29 mm(range,3.52-6.56 mm).HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas.Dogs in the study group did not exhibit obvious coughing after surgery.X-ray examination 2 wk after surgery indicated fixed magnet positioning,and gastroscopy showed no change in magnet positioning.The magnets were removed using a snare under endoscopy,and TEF was observed.Gross specimens showed well-formed fistulas with a diameter of 6.11 mm±0.16 mm(range,5.92-6.36 mm),which exceeded that in the control group(P<0.001).Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining,and the structure was more regular than that in the control group.CONCLUSION Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets.Most importantly,this model offers better controllability,which improves the flexibility of follow-up studies.
基金the Fundamental Research Funds for the Central Universities,National Natural Science Foundation of China(No.82302345).
文摘In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases.Currently,implantable electrochemical microsensors have emerged as a prominent area of research.These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration.They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner,characterized by their bloodless,painless features,and exceptional performance.The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts.This review commenced with a comprehensive discussion of the construction of microsensors,including the materials utilized and the methods employed for fabrication.Following this,we proceeded to explore the various implantation technologies employed for electrochemical microsensors.In addition,a comprehensive overview was provided of the various applications of implantable electrochemical microsensors,specifically in the monitoring of diseases and the investigation of disease mechanisms.Lastly,a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.
基金supported by the Cutting Edge Development Fund of Advanced Medical Research Institute(GYY2023QY01)the China Postdoctoral Science Foundation(certificate number:2023M732093)。
文摘Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.
文摘Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.