Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an imp...BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.展开更多
BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated ...BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.展开更多
Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory ...Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.展开更多
To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under ...To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under the conditions of a 2.4 m×2.4 m transonic wind tunnel with porous wall.From the CFD simulations of the flows through an inclined hole of this wind tunnel,the Nambu's linear porous wall model between the flow rate and the differential pressure is extended to the porous wall with inclined holes,so that the porous wall can be conveniently modeled as a boundary condition.According to the flutter testing approach for the current wind tunnel,the steady CFD calculation is conducted to achieve the required inlet Mach number.A timedomain CFD/CSD method is then employed to evaluate the structural response of the experimental model,and the critical flutter point is obtained by increasing the dynamic pressure step by step at a fixed Mach number.The present method is applied to the flutter calculations for a vertical tail model and an aircraft model tested in the current transonic wind tunnel.For both models,the computed flutter characteristics agree well with the experimental results.展开更多
This article aims tomodel and analyze the heat and fluid flow characteristics of a carboxymethyl cellulose(CMC)nanofluid within a convergent-divergent shaped microchannel(Two-dimensional).The base fluid,water+CMC(0.5%...This article aims tomodel and analyze the heat and fluid flow characteristics of a carboxymethyl cellulose(CMC)nanofluid within a convergent-divergent shaped microchannel(Two-dimensional).The base fluid,water+CMC(0.5%),is mixed with CuO and Al2O3 nanoparticles at volume fractions of 0.5%and 1.5%,respectively.The research is conducted through the conjugate usage of experimental and theoretical models to represent more realistic properties of the non-Newtonian nanofluid.Three types of microchannels including straight,divergent,and convergent are considered,all having the same length and identical inlet cross-sectional area.Using ANSYS FLUENT software,Navier-Stokes equations are solved for the laminar flow of the non-Newtonian nanofluid.The study examines the effects of Reynolds number,nanoparticle concentration and type,and microchannel geometry on flow and heat transfer.The results prove that the alumina nanoparticles outperform copper oxide in increasing the Nusselt number at a 0.5% volume fraction,while copper oxide nanoparticles excel at a 1.5%volume fraction.Moreover,in the selected case study,as the Reynolds number increases from 100 to 500,the Nusselt number rises by 56.26% in straight geometry,52.93% in divergent geometry,and 59.10%in convergent geometry.Besides,the Nusselt number enhances by 18.75% when transitioning from straight to convergent geometry at a Reynolds number of 500,and by 19.81%at a Reynolds number of 1000.Finally,the results of the research depict that the use of thermophysical properties derived from the experimental achievements,despite creating complexity in the modeling and the solution method,leads to more accurate and realistic outputs.展开更多
Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extra...Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.展开更多
Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chron...Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.展开更多
Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the num...Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.展开更多
Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the num...Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.展开更多
Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(...Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.展开更多
Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and bra...Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.展开更多
Fishing boats are usually anchored side by side in the harbor because of the small structural size and poor resistance to wind and waves.A series of physical model experiments are conducted to investigate the motion c...Fishing boats are usually anchored side by side in the harbor because of the small structural size and poor resistance to wind and waves.A series of physical model experiments are conducted to investigate the motion characteristics of multiple fishing boats that are moored together.A decay test in calm water is conducted to study the natural period and damping coefficients.Regular wave experiments are performed to analyze the roll motion response of each boat for four modes(different numbers of boats side-by-side).The results indicate that the“natural period”of each boat for the mode of multi-boats especially three or four boats,is slightly smaller than that of a single boat,whereas the damping coefficient is visibly larger than that of a single boat.The maximum roll angle of each boat does not appear at the same time under a 90°incident wave.Small roll motion energy is generated at low frequencies and high frequencies when multiple boats are moored together.The energy decreases with the increasing wave period.The roll motion responses of each boat in four modes exhibit different trends with the increasing wave frequency.The number of boats and boat position have significant effects on roll motion.展开更多
With the acceleration of marine construction in China,the exploitation and utilization of resources from islands and reefs are necessary.To prevent and dissipate waves in the process of resource exploitation and utili...With the acceleration of marine construction in China,the exploitation and utilization of resources from islands and reefs are necessary.To prevent and dissipate waves in the process of resource exploitation and utilization,a more effective method is to install floating breakwaters near the terrain of islands and reefs.The terrain around islands and reefs is complex,and waves undergo a series of changes due to the impact of the complex terrain in transmission.It is important to find a suitable location for floating breakwater systems on islands and reefs and investigate how the terrain affects the system’s hydrodynamic performance.This paper introduces a three-cylinder floating breakwater design.The breakwater system consists of 8 units connected by elastic structures and secured by a slack mooring system.To evaluate its effectiveness,a 3D model experiment was conducted in a wave basin.During the experiment,a model resembling the islands and reefs terrain was created on the basis of the water depth map of a specific region in the East China Sea.The transmission coefficients and motion responses of the three-cylinder floating breakwater system were then measured.This was done both in the middle of and behind the islands and reefs terrain.According to the experimental results,the three-cylinder floating breakwater system performs better in terms of hydrodynamics when it is placed behind the terrain of islands and reefs than in the middle of the same terrain.展开更多
Breast cancer metastasis is a major cause of treatment failure and patient mortality. Mouse tumor models largely replicate the pathophysiological processes of human tumors. Establishing mouse models of breast cancer m...Breast cancer metastasis is a major cause of treatment failure and patient mortality. Mouse tumor models largely replicate the pathophysiological processes of human tumors. Establishing mouse models of breast cancer metastasis helps to elucidate metastatic mechanisms, and in vivo imaging techniques enable dynamic monitoring of tumor cell metastasis in animals. This paper summarizes the mechanisms of breast cancer metastasis, the development, and application of various mouse breast cancer distant metastasis models over the past decade, and evaluates the characteristics and efficacy of each model to provide references for future experimental studies.展开更多
Chronic lower back pain(LBP)is the leading cause of disability worldwide.Due to its close relationship with intervertebral disc(IVD)degeneration(IVDD),research has historically focused more on understanding the mechan...Chronic lower back pain(LBP)is the leading cause of disability worldwide.Due to its close relationship with intervertebral disc(IVD)degeneration(IVDD),research has historically focused more on understanding the mechanism behind IVDD while clinical efforts prioritize pain management.More recently,there has been a shift toward understanding LBP as a distinct pathological entity.This review synthesizes current knowledge on discogenic LBP,combining known pathophysiology,molecular mechanisms,risk factors,diagnostic challenges,and available experimental models.IVDD is a complex,multifactorial process involving biochemical,mechanical,and inflammatory changes within the disc,leading to structural breakdown and potential discogenic pain.Key mechanisms include extracellular matrix degradation,upregulation of inflammatory mediators,immune cell infiltration,and aberrant nerve and vascular ingrowth.However,not all cases of IVDD result in LBP,highlighting the need for further investigation into the cellular,molecular,and biomechanical factors contributing to symptom development.Current diagnostic tools and experimental models for studying discogenic LBP remain limited,impeding the development of targeted treatments.Existing therapies primarily focus on symptom management rather than addressing underlying disease mechanisms.展开更多
Background:Medulloblastoma(MB)is one of the most common malignant brain tumors that mainly affect children.Various approaches have been used to model MB to facilitate investigating tumorigenesis.This study aims to com...Background:Medulloblastoma(MB)is one of the most common malignant brain tumors that mainly affect children.Various approaches have been used to model MB to facilitate investigating tumorigenesis.This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft(sPDX),intracranial patient-derived xenograft(iPDX),and genetically engineered mouse models(GEMM)at the single-cell level.Methods:We obtained primary human sonic hedgehog(SHH)and group 3(G3)MB samples from six patients.For each patient specimen,we developed two sPDX and iPDX models,respectively.Three Patch+/-GEMM models were also included for sequencing.Single-cell RNA sequencing was performed to compare gene expression profiles,cellular composition,and functional pathway enrichment.Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples.Results:Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups,followed by the GEMM model and iPDX.The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment(TME)cells that can be clustered in human SHH tumors,including a higher proportion of tumor-associated astrocytes and immune cells,and an additional cluster of vascular endothelia when compared to human SHH tumors.Conclusions:This study was the first to compare experimental models for MB at the single-cell level,providing value insights into model selection for different research purposes.sPDX and iPDX are suitable for drug testing and personalized therapy screenings,whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.展开更多
In order to check the validity of the mathematical model for analyzing the flow field in the air-agitated seed precipitation tank,a scaled down experimental apparatus was designed and the colored tracer and KCl tracer...In order to check the validity of the mathematical model for analyzing the flow field in the air-agitated seed precipitation tank,a scaled down experimental apparatus was designed and the colored tracer and KCl tracer were added in the apparatus to follow the real flow line.Virtue tracers were considered in the mathematical model and the algorithm of tracers was built.The comparison of the results between the experiment and numerical calculation shows that the time of the tracer flows out of stirring tube are 40 s in the experiment and 42 s in numerical calculated result.The transient diffusion process and the solution residence time of the numerical calculation are in good agreement with the experimental results,which indicates that the mathematical model is reliable and can be used to predict the flow field of the air-agitated seed precipitation tank.展开更多
Beishan Rock Carvings in Chongqing,a renowned cultural heritage site in China,flourished during the Tang and Song dynasties and are often referred to as the“Stone Carving Art Museum of the Tang and Song Dynasties.”C...Beishan Rock Carvings in Chongqing,a renowned cultural heritage site in China,flourished during the Tang and Song dynasties and are often referred to as the“Stone Carving Art Museum of the Tang and Song Dynasties.”Cave 168 is a key component of the Beishan Rock Carvings.At present,several through-going cracks have developed in the roof of Cave 168,severely compromising the structural stability of the grotto.The early internal steel plate supports have suffered severe corrosion and can no longer provide effective reinforcement.In addition,the presence of steel columns obstructs visitor access and negatively affects the viewing experience.A new reinforcement method is urgently needed.Therefore,studying the deformation patterns of the structure is of critical importance.This study analyzes the stratigraphic parameters and fracture distribution of Cave 168,considering key influencing factors such as rainfall,self-weight,and the overlying Quaternary soil.On-site monitoring and physical model experiments were conducted to evaluate the changes in roof crack width and displacement before and after reinforcement with negative Poisson's ratio(NPR)anchor cables.The results reveal that the roof of Cave 168 contains several through-going cracks and numerous microcracks,which serve as infiltration channels for surface water.These accelerate the softening of the mudstone and pose a significant threat to the cave's structural safety.During the experiment,the main change in the crack exhibited a“semi-archshaped”propagation pattern.In the first ten minutes,as the rock transitioned from dry to moist conditions,a slight crack closure was observed.As rainfall continued,crack propagation accelerated.After rainfall ceased,crack width remained stable over a short period.Under NPR anchor support,the influence of rainfall on roof settlement was effectively mitigated,ensuring the safety and stability of the roof.The NPR anchors successfully limited the roof settlement to within 0.3 mm and provided effective control over both total and differential settlement.These findings offer valuable insights into the application of NPR anchor cables in the conservation of grotto heritage structures.展开更多
Objective The present study aimed to establish a cerebral schistosomiasis model in rabbits,to provide a valuable tool for morphological analysis,clinical manifestation observation,as well as investigations into immuno...Objective The present study aimed to establish a cerebral schistosomiasis model in rabbits,to provide a valuable tool for morphological analysis,clinical manifestation observation,as well as investigations into immunological reactions and pathogenesis of focal inflammatory reaction in neuroschistosomiasis（NS）.Methods Sixty New Zealand rabbits were randomly assigned into operation,sham-operation and normal groups.Rabbits in the operation group received direct injection of dead schistosome eggs into the brain,while their counterparts in the sham-operation group received saline injection.Rabbits in the normal group received no treatment.Base on the clinical manifestations,rabbits were sacrificed on days 3,5,7,10,20,and 30 post injection,and brain samples were sectioned and stained with hematoxylin-eosin.Sections were observed under the microscope.Results The rabbits in the operation group exhibited various neurological symptoms,including anorexy,partial and general seizures,and paralysis.The morphological analysis showed several schistosome eggs in the nervous tissue on day 3 post operation,with very mild inflammation.On days 7-10 post operation,several schistosome eggs were localized in proximity to red blood cells with many neutrophilic granulocytes and eosinophilic granulocytes around them.The schistosome eggs developed into the productive granuloma stage on days 14-20 post operation.On day 30,the schistosome eggs were found to be in the healing-by-fibrosis stage,and the granuloma area was replaced by fibrillary glia through astrocytosis.The sham-operation group and the normal group showed negative results.Conclusion This method might be used to establish the cerebral schistosomiasis experimental model.Several factors need to be considered in establishing this model,such as the antigenic property of eggs,the time of scarification,and the clinical manifestations.展开更多
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
文摘BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.
基金Supported by National Natural Science Foundation of China,No.82260133 and No.82370661the Academic and Technical Leader of major disciplines in Jiangxi Province,No.20225BCJ23021+2 种基金the Jiangxi Medicine Academy of Nutrition and Health Management,No.2022-PYXM-01the Natural Science Foundation of Jiangxi Province,No.20224ACB216004the Technological Innovation Team Cultivation Project of the First Affiliated Hospital of Nanchang University,No.YFYKCTDPY202202.
文摘BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.
基金supported by the China Postdoctoral Science Foundation (no. 2020M670599)
文摘Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.
基金supported by the National Natural Science Foundation of China(No.11872212)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under the conditions of a 2.4 m×2.4 m transonic wind tunnel with porous wall.From the CFD simulations of the flows through an inclined hole of this wind tunnel,the Nambu's linear porous wall model between the flow rate and the differential pressure is extended to the porous wall with inclined holes,so that the porous wall can be conveniently modeled as a boundary condition.According to the flutter testing approach for the current wind tunnel,the steady CFD calculation is conducted to achieve the required inlet Mach number.A timedomain CFD/CSD method is then employed to evaluate the structural response of the experimental model,and the critical flutter point is obtained by increasing the dynamic pressure step by step at a fixed Mach number.The present method is applied to the flutter calculations for a vertical tail model and an aircraft model tested in the current transonic wind tunnel.For both models,the computed flutter characteristics agree well with the experimental results.
文摘This article aims tomodel and analyze the heat and fluid flow characteristics of a carboxymethyl cellulose(CMC)nanofluid within a convergent-divergent shaped microchannel(Two-dimensional).The base fluid,water+CMC(0.5%),is mixed with CuO and Al2O3 nanoparticles at volume fractions of 0.5%and 1.5%,respectively.The research is conducted through the conjugate usage of experimental and theoretical models to represent more realistic properties of the non-Newtonian nanofluid.Three types of microchannels including straight,divergent,and convergent are considered,all having the same length and identical inlet cross-sectional area.Using ANSYS FLUENT software,Navier-Stokes equations are solved for the laminar flow of the non-Newtonian nanofluid.The study examines the effects of Reynolds number,nanoparticle concentration and type,and microchannel geometry on flow and heat transfer.The results prove that the alumina nanoparticles outperform copper oxide in increasing the Nusselt number at a 0.5% volume fraction,while copper oxide nanoparticles excel at a 1.5%volume fraction.Moreover,in the selected case study,as the Reynolds number increases from 100 to 500,the Nusselt number rises by 56.26% in straight geometry,52.93% in divergent geometry,and 59.10%in convergent geometry.Besides,the Nusselt number enhances by 18.75% when transitioning from straight to convergent geometry at a Reynolds number of 500,and by 19.81%at a Reynolds number of 1000.Finally,the results of the research depict that the use of thermophysical properties derived from the experimental achievements,despite creating complexity in the modeling and the solution method,leads to more accurate and realistic outputs.
基金United Arab Emirates University,Grant/Award Number:12R104 and 12R121。
文摘Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
文摘Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.
基金supported by grants from the from the Department of Defense Breast Cancer Research Program(CA171885)from the National Cancer Institute(U01CA184902)to Dr.Clarke.
文摘Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
基金This work was supported by grants from the from the Department of Defense Breast Cancer Research Program(CA171885)from the National Cancer Institute(U01CA184902)to Dr.Clarke.
文摘Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
基金Supported by the Austrian EURASIA-PACIFIC UNINET Technology Scholarship,the Austrian Federal Ministry of Science and Research and the Austrian Federal Ministry of Health(GZ 402.000/0006-II/6b/2012)the National Basic Research Program of China(No.2014CB543203)
文摘Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.
基金supported by the National Natural Science Foundation of China(81825011,81930038,81961160738)Program of Shanghai Academic/Technology Research Leader(22XD1400800)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19030200)。
文摘Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.
基金financially supported by Central Public-interest Scientific Institution Basal Research Fund,CAFS(Grant Nos.2023TD88,2024HY-ZC005,and 2024XT0801).
文摘Fishing boats are usually anchored side by side in the harbor because of the small structural size and poor resistance to wind and waves.A series of physical model experiments are conducted to investigate the motion characteristics of multiple fishing boats that are moored together.A decay test in calm water is conducted to study the natural period and damping coefficients.Regular wave experiments are performed to analyze the roll motion response of each boat for four modes(different numbers of boats side-by-side).The results indicate that the“natural period”of each boat for the mode of multi-boats especially three or four boats,is slightly smaller than that of a single boat,whereas the damping coefficient is visibly larger than that of a single boat.The maximum roll angle of each boat does not appear at the same time under a 90°incident wave.Small roll motion energy is generated at low frequencies and high frequencies when multiple boats are moored together.The energy decreases with the increasing wave period.The roll motion responses of each boat in four modes exhibit different trends with the increasing wave frequency.The number of boats and boat position have significant effects on roll motion.
基金financially supported by the China National Funds for Distinguished Young Scientists(Grant No.52025112).
文摘With the acceleration of marine construction in China,the exploitation and utilization of resources from islands and reefs are necessary.To prevent and dissipate waves in the process of resource exploitation and utilization,a more effective method is to install floating breakwaters near the terrain of islands and reefs.The terrain around islands and reefs is complex,and waves undergo a series of changes due to the impact of the complex terrain in transmission.It is important to find a suitable location for floating breakwater systems on islands and reefs and investigate how the terrain affects the system’s hydrodynamic performance.This paper introduces a three-cylinder floating breakwater design.The breakwater system consists of 8 units connected by elastic structures and secured by a slack mooring system.To evaluate its effectiveness,a 3D model experiment was conducted in a wave basin.During the experiment,a model resembling the islands and reefs terrain was created on the basis of the water depth map of a specific region in the East China Sea.The transmission coefficients and motion responses of the three-cylinder floating breakwater system were then measured.This was done both in the middle of and behind the islands and reefs terrain.According to the experimental results,the three-cylinder floating breakwater system performs better in terms of hydrodynamics when it is placed behind the terrain of islands and reefs than in the middle of the same terrain.
基金Hebei Province Natural Science Foundation Key Project(H2024104001)Hebei Province Medical Science Research Project Plan(20240287)。
文摘Breast cancer metastasis is a major cause of treatment failure and patient mortality. Mouse tumor models largely replicate the pathophysiological processes of human tumors. Establishing mouse models of breast cancer metastasis helps to elucidate metastatic mechanisms, and in vivo imaging techniques enable dynamic monitoring of tumor cell metastasis in animals. This paper summarizes the mechanisms of breast cancer metastasis, the development, and application of various mouse breast cancer distant metastasis models over the past decade, and evaluates the characteristics and efficacy of each model to provide references for future experimental studies.
基金supported by the California Institute for Regenerative Medicine under EDUC4-12751(Giselle Kaneda)DISC2-14049(Dmitriy Sheyn)+1 种基金Additional support was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers R01AR066517(Debiao Li)R01AR082041(Dmitriy Sheyn).
文摘Chronic lower back pain(LBP)is the leading cause of disability worldwide.Due to its close relationship with intervertebral disc(IVD)degeneration(IVDD),research has historically focused more on understanding the mechanism behind IVDD while clinical efforts prioritize pain management.More recently,there has been a shift toward understanding LBP as a distinct pathological entity.This review synthesizes current knowledge on discogenic LBP,combining known pathophysiology,molecular mechanisms,risk factors,diagnostic challenges,and available experimental models.IVDD is a complex,multifactorial process involving biochemical,mechanical,and inflammatory changes within the disc,leading to structural breakdown and potential discogenic pain.Key mechanisms include extracellular matrix degradation,upregulation of inflammatory mediators,immune cell infiltration,and aberrant nerve and vascular ingrowth.However,not all cases of IVDD result in LBP,highlighting the need for further investigation into the cellular,molecular,and biomechanical factors contributing to symptom development.Current diagnostic tools and experimental models for studying discogenic LBP remain limited,impeding the development of targeted treatments.Existing therapies primarily focus on symptom management rather than addressing underlying disease mechanisms.
基金National Key Research and Development Program of China,Grant/Award Number:2022ZD0210100Beijing Nova Star Program,Grant/Award Number:2022002+2 种基金Natural Science Foundation of Beijing and Haidian Collaboration Foundation,Grant/Award Number:L232079National Natural Science Foundation of China,Grant/Award Number:82172608,82273343,81902975 and 82101356Capital Medical University Fund for Excellent Young Scholars,Grant/Award Number:KCB2304。
文摘Background:Medulloblastoma(MB)is one of the most common malignant brain tumors that mainly affect children.Various approaches have been used to model MB to facilitate investigating tumorigenesis.This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft(sPDX),intracranial patient-derived xenograft(iPDX),and genetically engineered mouse models(GEMM)at the single-cell level.Methods:We obtained primary human sonic hedgehog(SHH)and group 3(G3)MB samples from six patients.For each patient specimen,we developed two sPDX and iPDX models,respectively.Three Patch+/-GEMM models were also included for sequencing.Single-cell RNA sequencing was performed to compare gene expression profiles,cellular composition,and functional pathway enrichment.Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples.Results:Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups,followed by the GEMM model and iPDX.The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment(TME)cells that can be clustered in human SHH tumors,including a higher proportion of tumor-associated astrocytes and immune cells,and an additional cluster of vascular endothelia when compared to human SHH tumors.Conclusions:This study was the first to compare experimental models for MB at the single-cell level,providing value insights into model selection for different research purposes.sPDX and iPDX are suitable for drug testing and personalized therapy screenings,whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.
基金Project(07JJ4016) supported by the Natural Science Foundation of Hunan Procvince,China
文摘In order to check the validity of the mathematical model for analyzing the flow field in the air-agitated seed precipitation tank,a scaled down experimental apparatus was designed and the colored tracer and KCl tracer were added in the apparatus to follow the real flow line.Virtue tracers were considered in the mathematical model and the algorithm of tracers was built.The comparison of the results between the experiment and numerical calculation shows that the time of the tracer flows out of stirring tube are 40 s in the experiment and 42 s in numerical calculated result.The transient diffusion process and the solution residence time of the numerical calculation are in good agreement with the experimental results,which indicates that the mathematical model is reliable and can be used to predict the flow field of the air-agitated seed precipitation tank.
文摘Beishan Rock Carvings in Chongqing,a renowned cultural heritage site in China,flourished during the Tang and Song dynasties and are often referred to as the“Stone Carving Art Museum of the Tang and Song Dynasties.”Cave 168 is a key component of the Beishan Rock Carvings.At present,several through-going cracks have developed in the roof of Cave 168,severely compromising the structural stability of the grotto.The early internal steel plate supports have suffered severe corrosion and can no longer provide effective reinforcement.In addition,the presence of steel columns obstructs visitor access and negatively affects the viewing experience.A new reinforcement method is urgently needed.Therefore,studying the deformation patterns of the structure is of critical importance.This study analyzes the stratigraphic parameters and fracture distribution of Cave 168,considering key influencing factors such as rainfall,self-weight,and the overlying Quaternary soil.On-site monitoring and physical model experiments were conducted to evaluate the changes in roof crack width and displacement before and after reinforcement with negative Poisson's ratio(NPR)anchor cables.The results reveal that the roof of Cave 168 contains several through-going cracks and numerous microcracks,which serve as infiltration channels for surface water.These accelerate the softening of the mudstone and pose a significant threat to the cave's structural safety.During the experiment,the main change in the crack exhibited a“semi-archshaped”propagation pattern.In the first ten minutes,as the rock transitioned from dry to moist conditions,a slight crack closure was observed.As rainfall continued,crack propagation accelerated.After rainfall ceased,crack width remained stable over a short period.Under NPR anchor support,the influence of rainfall on roof settlement was effectively mitigated,ensuring the safety and stability of the roof.The NPR anchors successfully limited the roof settlement to within 0.3 mm and provided effective control over both total and differential settlement.These findings offer valuable insights into the application of NPR anchor cables in the conservation of grotto heritage structures.
基金supported by the Science Foundation of the Department of Health,Hubei Province,China (No.XF06D43,XF2008-23)
文摘Objective The present study aimed to establish a cerebral schistosomiasis model in rabbits,to provide a valuable tool for morphological analysis,clinical manifestation observation,as well as investigations into immunological reactions and pathogenesis of focal inflammatory reaction in neuroschistosomiasis（NS）.Methods Sixty New Zealand rabbits were randomly assigned into operation,sham-operation and normal groups.Rabbits in the operation group received direct injection of dead schistosome eggs into the brain,while their counterparts in the sham-operation group received saline injection.Rabbits in the normal group received no treatment.Base on the clinical manifestations,rabbits were sacrificed on days 3,5,7,10,20,and 30 post injection,and brain samples were sectioned and stained with hematoxylin-eosin.Sections were observed under the microscope.Results The rabbits in the operation group exhibited various neurological symptoms,including anorexy,partial and general seizures,and paralysis.The morphological analysis showed several schistosome eggs in the nervous tissue on day 3 post operation,with very mild inflammation.On days 7-10 post operation,several schistosome eggs were localized in proximity to red blood cells with many neutrophilic granulocytes and eosinophilic granulocytes around them.The schistosome eggs developed into the productive granuloma stage on days 14-20 post operation.On day 30,the schistosome eggs were found to be in the healing-by-fibrosis stage,and the granuloma area was replaced by fibrillary glia through astrocytosis.The sham-operation group and the normal group showed negative results.Conclusion This method might be used to establish the cerebral schistosomiasis experimental model.Several factors need to be considered in establishing this model,such as the antigenic property of eggs,the time of scarification,and the clinical manifestations.
