Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

Dynamics and synchronization of neural models with memristive membranes under energy coupling

Dynamical modeling of neural systems plays an important role in explaining and predicting some features of biophysical mechanisms.The electrophysiological environment inside and outside of the nerve cell is different.Due to the continuous and periodical properties of electromagnetic fields in the cell during its operation,electronic components involving two capacitors and a memristor are effective in mimicking these physical features.In this paper,a neural circuit is reconstructed by two capacitors connected by a memristor with periodical mem-conductance.It is found that the memristive neural circuit can present abundant firing patterns without stimulus.The Hamilton energy function is deduced using the Helmholtz theorem.Further,a neuronal network consisting of memristive neurons is proposed by introducing energy coupling.The controllability and flexibility of parameters give the model the ability to describe the dynamics and synchronization behavior of the system.

A new liquid membrane diffusion model for characterizing the adsorption kinetics of europium by using a continuous measurement of adsorption platform

To explore the kinetic adsorption under continuous and nonequilibrium states, an integration of continuous measurement and adsorption platform kinetics method was proposed, which was initially called the ICM-AP kinetics method, and a corresponding kinetic adsorption experimental method was developed. Adsorption experiments of europium(Eu) on Ca-bentonite,Na-bentonite, and the D231 cation exchange resin were performed using the ICM-AP kinetics method and continuous measurements. Because the kinetic experimental results observed in this study were different from those of traditional batch adsorption data, pseudo-first-order or pseudo-second-order kinetic models were unsuitable for fitting the experimental data.Hence, a liquid membrane diffusion(LMD) model was developed based on the assumption of simultaneous adsorption/desorption to discuss the mechanism of kinetic adsorption. The kinetic adsorption mechanism was also studied by using XPS.The results indicated that the proposed adsorption model can fit the experimental data more suitably, and the adsorption/desorption behaviors of Eu on bentonite and the D231 resin were simultaneously observed, suggesting that the adsorption kinetics of Eu(Ⅲ) was mainly dominated by hydrated Eu(Ⅲ) ions on the liquid membrane.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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.

Exploiting fly models to investigate rare human neurological disorders

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

Effects of BYHW Decoction and Its Effective Constituents on the Fluidity of the Cell Membrane in a Stroke-Modeled Rat Brain

With in vitro spin labeling electron spin resonance (ESR) spectroscopy, we have studied the effects of Bu Yang Huan Wu (BYHW) decoction and its effective constituents such as astragaloside IV ferulic acid, chuanxiongzine, rutin, chlorogenic acid, 9,10 dimethoxy pterocarpane 7 O β D glucoside, calycosin, formononetin, calycosin 7 O glucoside, paeoniflorin, paeonal and quercein on the cell membrane fluidity of a rat brain which was modeled after the dual cervical arteries were intercepted and released for realizing an ischemia reperfusion injury which was selected as a brain stroke model. Our results indicated that the cell membrane fluidity in the model group decreased approximately 8% compared with the control group, and after brain cells were incubatied with species, the membrane fluidity could be recovered closely to the control level depending on the BYHW decoction and its different constituents. As the membrane fluidity is a very sensitive biological index which reflectsd the cell status, our method will be useful to study the molecular mechanism of tradition Chinese medicine (TCM) and its combination recipe.

Analytical model for power dissipation in cell membranes in suspensions exposed to electric fields

Due to interaction among cells, it is too complex to build an exactanalytical model for the power dissipation within the cell membrane in suspensions exposed toexternal fields. An approximate equivalence method is proposed to resolve this problem. Based on theeffective medium theory, the transmembrane voltage on cells in suspensions was investigated by theequivalence principle. Then the electric field in the cell membrane was determined. Finally,analytical solutions for the power dissipation within the cell membrane in suspensions exposed toexternal fields were derived according to the Joule principle. The equations show that theconductive power dissipation is predominant within the cell membrane in suspensions exposed todirect current or lower frequencies, and dielectric power dissipation prevails at high frequenciesexceeding the relaxation frequency of the exposed membrane.

采用STAMP-24Model的多组织事故分析

安全生产事故往往由多组织交互、多因素耦合造成,事故原因涉及多个组织。为预防和遏制多组织生产安全事故的发生,基于系统理论事故建模与过程模型(Systems-Theory Accident Modeling and Process,STAMP)、24Model,构建一种用于多组织事故分析的方法,并以青岛石油爆炸事故为例进行事故原因分析。结果显示:STAMP-24Model可以分组织,分层次且有效、全面、详细地分析涉及多个组织的事故原因,探究多组织之间的交互关系;对事故进行动态演化分析,可得到各组织不安全动作耦合关系与形成的事故失效链及管控失效路径,进而为预防多组织事故提供思路和参考。

Methanol Perturbing Modeling Cell Membranes Investigated using Linear and Nonlinear Vibrational Spectroscopy

Cell membranes play a crucial role in many biological functions of cells. A small change in the composition of cell membranes can strongly influence the functions of membrane-associated proteins, such as ion and water channels, and thus mediate the chemical and physical balance in cells. Such composition change could originate from the introduction of short-chain alcohols, or other anesthetics into membranes. In this work, we have applied sum frequency generation vibrational spectroscopy （SFG-VS）, supplemented by attenuated total reflectance Fourier transform infrared spectroscopy （ATR-FTIR）, to investigate interaction between methanol and 1,2-dimyristoyl-d54-sn-glycero-3-phosphocholine （d54-DMPC） lipid bilayers. Lipid＇s hydrocarbon interior is deuterated while its head group is hydrogenated. At the same time, CH3 symmetric stretch from methanol and lipid head amine group has different frequency, thus we can distinguish the behaviors of methanol, lipid head amine group, and lipid hydrocarbon interior. Based on the spectral feature of the bending mode of the water molecules replaced by methanol, we determined that the methanol molecules are intercalated into the region between amine and phosphate groups at the lipid hydrophilic head. The dipole of CH3 groups of methanol and lipid head, and the water O-H M1 adopt the same orientation directions. The introduction of methanol into the lipid hydrophilic head group can strongly perturb the entire length of the alkyl chains, resulting that the signals of CD2 and CD3 groups from both leaflets can not cancel each other.

Experimental Study and Model Analysis of the Performance of IPMC Membranes with Various Thickness

Ionic Polymer-Metal Composite （IPMC） is a new electro-active polymer, which has the advantages of light weight, flexibility, and large stroke with low driving voltage. Because of these features, IPMC can be applied to bionic robotic actuators, artificial muscles, as well as dynamic sensors. However, IPMC has the major drawback of low generative blocking force. In this paper, in order to enhance the blocking force, the Nation membranes with thickness of 0.22 mm, 0.32 mm, 0.42 mm, 0.64 mm and 0.8 mm were prepared by casting from liquid solution. By employing these Nation membranes, IPMCs with varying thickness were fabricated by electroless plating. The elastic modulus of the casted Nation membranes were obtained by a nano-indenter, and the current, the displacement and the blocking force were respectively measured by the apparatus for actuation test. Finally, the effects of the thickness on the performance of IPMC were analyzed with an electromechanical model. Experimental study and theory analysis indicate that as the thickness increases, the elastic modulus of Nation membrane and the blocking force of IPMC increase, however, the current and the displacement decrease.

基于改进24Model-ISM-SNA建筑工人不安全行为关联路径研究

建筑施工现场环境复杂,为有效控制不安全行为发生,基于行为安全“2-4”模型对360份具有代表性的建筑安全事故调查报告进行分析,提取出22个不安全行为的主要影响因素。利用灰色关联分析方法(GRA)改进的集成ISM-SNA模型,将不安全行为风险因素划分为表层、过渡层与深层,然后对风险因素进行可视化分析、中心度分析及凝聚子群分析,揭示了各致因因素间的关联关系和传导路径。结果表明,建筑工人不安全行为影响因素可划分成7级3阶的多级递阶结构,安全意识、现场监管、外部环境是建筑工人不安全行为的关键影响因素,同时现场监管和隐患排查到位能有效降低不安全行为的发生。

Strain and stress variations in the human amniotic membrane and fresh corpse autologous sciatic nerve anastomosis in a model of sciatic nerve injury

A 10-mm long sciatic nerve injury model was established in fresh normal Chinese patient cadavers. Amniotic membrane was harvested from healthy maternal placentas and was prepared into multilayered,coiled,tubular specimens.Sciatic nerve injury models were respectively anastomosed using the autologous cadaveric sciatic nerve and human amniotic membrane.Tensile test results showed that maximal loading,maximal displacement,maximal stress,and maximal strain of sciatic nerve injury models anastomosed with human amniotic membrane were greater than those in the autologous nerve anastomosis group.The strain-stress curves of the human amniotic membrane and sciatic nerves indicated exponential change at the first phase,which became elastic deformation curves at the second and third phases,and displayed plastic deformation curves at the fourth phase,at which point the specimens lost their bearing capacity.Experimental findings suggested that human amniotic membranes and autologous sciatic nerves exhibit similar stress-strain curves, good elastic properties,and certain strain and stress capabilities in anastomosis of the injured sciatic nerve.

基于24Model的地铁内涝事故原因分析与评估

为降低地铁内涝事故灾害风险,基于事故致因“2-4”模型,分析了地铁内涝事故致灾因子,采用层次分析法构建了地铁内涝事故原因分析指标体系,确定了各风险因子的权重,并利用模糊综合评价法对地铁内涝事故进行了定量评估,识别出关键的影响因素。结果表明:地铁内涝事故一级指标中不安全动作与物态因素最重要,其中影响最大的指标包括擅自更改建筑设计、未按照要求检查水位情况、未及时排水、出入口不符合防汛标准等因素;习惯性不安全行为的权重位居第二,表明该指标因素较为重要,同时安全管理体系得分位居第二,表明该指标因素较易发生。对关键指标采取防范措施,可有效降低风险,从而减少地铁内涝事故的发生。

Mass transfer model,preparation and applications of zeolite membranes for pervaporation dehydration:A review

Pervaporation(including vapor permeation) is a kind of new membrane separation technology, possessing the advantages of high efficiency, energy saving and convenient operation. It has promising application in the separation and purification of organic solvents. Dehydration is an important step in the production and recovery of organic solvents. Zeolite membranes have attracted wide attention for pervaporation dehydration due to their high separation performance and good thermal/chemical stability. So far, zeolite membranes have been preliminarily industrialized for dehydration of organic solvents. This paper reviews the recent development of zeolite membranes for pervaporation dehydration, including mass transfer models, preparation and applications of zeolite membranes. The review also discusses the current industrial applications of zeolite membranes and their future development in pervaporation.

Modelling the biological performance of a side-stream membrane bioreactor using ASM1

Membrane bioreactors(MBRs) are attracting global interest but the mathematical modeling of the biological performance of MBRs remains very limited. This study focuses on the modelling of a side-stream MBR system using Activated Sludge Model No.1(ASM1), and comparing the results with the modelling of traditional activated sludge processes. ASM1 parameters relevant for the long-term biological behaviour in MBR systems were calibrated(i.e. Y H=0.72gCOD/gCOD, Y A=0.25gCOD/gN, b H=0.25 d -1, b A=0.080 d -1 and f P=0.06), and generally agreed with the parameters in traditional activated sludge processes, with the exception that a higher autotrophic biomass decay rate was observed in the MBR. A sensitivity analysis for steady state operation and DO dynamics suggested that the biological performance of the MBR system(the sludge concentration, effluent quality and the DO dynamics) are very sensitive to the parameters(i.e. Y H, Y A, b H, b A, μ maxH and μ maxA), and influent wastewater components(X I, S S, X S, S NH).

基于24Model-D-ISM的地铁站火灾疏散影响因素研究

为预防地铁站火灾事故,深入了解地铁站火灾人员疏散影响因素间的内在联系与层次结构,基于第6版“2-4”模型(24Model)分析63起地铁站火灾疏散事故,充分考虑各个因素之间的交互作用,提取19个影响地铁站人员疏散的关键因素,建立地铁站火灾人员疏散影响因素指标体系;采用算子客观赋权法(C-OWA)改进决策试验与评价实验法(DEMATEL),确定地铁站火灾人员疏散的重要影响因素;在此基础上,采用解释结构模型(ISM)分析各个因素间的层次结构及相互作用路径,构建地铁站火灾人员疏散影响因素的多级递阶结构模型。研究结果表明:疏散引导、恐慌从众行为、人员拥挤为地铁站火灾人员疏散的关键影响因素;地铁站火灾人员疏散受表层因素、中间层因素、深层因素共同作用的影响,其中,疏散教育与培训、设施维护与检查、疏散预案等因素是根源影响因素,重视根源影响因素的改善有利于从本质上预防和控制事故的发生。

Modeling of the Relationship Between Pore Size Distribution and Thickness of Ceramic MF Membrane

The pore size distribution(PSD)measured by the gas bubble point(GBP)method ofceramic microfiltration(MF)membranes prepared by suspension technique was found to be signifi-cantly influenced by the membrane thickness.A culm-like model for pore structure was introduced tocharacterize the membrane pores instead of the conventional model which does not reflect the radiusvariation along the pore passages and is unable to explain the thickness effect on the membrane PSD.A laminate structure,taking the culm-like model for pore structure into consideration,was hypoth-esized for ceramic MF membranes.A mathematical model was then established to quantitativelydescribe the relationship between the membrane number PSD and the membrane thickness.Goodresults were obtained for the correlation of mean pore size and simulation of the PSD for ceramicMF membranes.

Feasibility and simulation model of a pilot scale membrane bioreactor for wastewater treatment and reuse from Chinese traditional medicine

The lack and pollution of water resource make wastewater reuse necessary. The pilot scale long-term tests for submerged membrane bioreactor were conducted to treat the effluents of anaerobic or aerobic treatment process for the high-strength Chinese traditional medicine wastewater. This article was focused on the feasibility of the wastewater treatment and reuse at shorter hydraulic retention time （HRT） of 5.0, 3.2 and 2.13 h. MLSS growth, membrane flux, vacuum values and chemical cleaning periods were also investigated. The experimental results of treating two-phase anaerobic treatment effluent demonstrated that the CODfilt was less than 100 mg/L when the influent COD was between 500-10000 mg/L at HRT of 5.0 h, which could satisfy the normal discharged standard in China. The experimental results to treat cross flow aerobic reactor effluent demonstrated that the average value of CODfilt was 17.28 mg/L when the average value of influent COD was 192.84 mg/L at HRT of 2.13 h during 106 d, which could completely meet the normal standard for water reuse. The maximum MLSS and MLVSS reached 24000 and 14500 mg/L at HRT of 3.2 h respectively. Membrane flux had maximal resume degrees of 94.7% at vacuum value of 0.02 MPa after cleaning. Chemical cleaning periods of membrane module were 150 d. A simulation model of operational parameters was also established based on the theory of back propagation neural network and linear regression of traditional mathematical model. The simulation model showed that the optimum operational parameters were suggested as follows： HRT was 5.0 h, SRT was 100 d, the range of COD loading rate was between 10.664-20.451 kg/（m3.d）, the range of MLSS was between 7543-13694 mg/L.