Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment

Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

Comparison of Stem Damage and Carbohydrate Composition in the Stem Juice between Sugarcane and Sweet Sorghum Harvested before and after Late Fall Frost

A late fall frost may significantly affect sugar crops’ stem sugar composition, yield and juice quality for biofuel and bioproduct manufacture. Research on the effects of late fall frost in sugarcane is well documented, but information is lacking for sweet sorghum. Three and six commercial cultivars of sugarcane and sweet sorghum, respectively, were selected and evaluated for exposure to a late fall frost (-2.8&degC) in Griffin, Georgia, USA. Under the same controlled environmental conditions in a screen house, the late fall frost induced more damage to sugarcane than sweet sorghum stems. The frost caused damage to sugarcane tissue and for juice to exude from stems, whereas similar behavior was not observed for sweet sorghum. In both sugarcane and sweet sorghum, the glucose/fructose ratio was significantly reduced, but this change may not be totally directly related to the frost effect. Overall, these initial results suggest that sweet sorghum may have a better tolerance to fall frost than sugarcane. Two sweet sorghum cultivars, Grassl and M81E, responded well to the late fall frost, and they can possibly be used as feedstocks for biofuel/bioproduct manufacture in areas susceptible to frosts including northern regions of the Southeastern US.

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.

Effects of music and music therapy on mood in neurological patients

Mood disorder and depressive syndromes represent a common comorbid condition in neurological disorders witha prevalence rate that ranges between 20% and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson's disease. Notwithstanding, these conditions are often under-diagnosed and under-treated in the clinical practice and negatively affect the functional recovery, the adherence to treatment, the quality of life, and even the mortality risk. In addition, a bidirectional association between depression and neurological disorders may be possible being that depressive syndromes may be considered as a risk factor for certain neurological diseases. Despite the large amount of evidence regarding the effects of music therapy(MT) and other musical interventions on different aspects of neurological disorders, no updated article reviewing outcomes such as mood, emotions, depression, activity of daily living and so on is actually available; for this reason, little is known about the effectiveness of music and MT on these important outcomes in neurological patients. The aim of this article is to provide a narrative review of the current literature on musical interventions and their effects on mood and depression in patients with neurological disorders. Searching on Pub Med and Psyc Info databases, 25 studies corresponding to the inclusion criteria have been selected; 11 of them assess the effects of music or MT in Dementia, 9 explore the efficacy on patients with Stroke, and 5 regard other neurological diseases like Multiple Sclerosis, Amyotrophic Lateral Sclerosis/motor neuron disease, Chronic quadriplegia, Parkinson's Disease, and Acquired Brain dysfunctions. Selected studies are based on relational and rehabilitative music therapy approaches or concern music listening interventions. Most of the studies support the efficacy of MT and other musical interventions on mood, depressive syndromes, and quality of life on neurological patients.

Rheological property of low-damage,ideal packing,film-forming amphoteric/sulfonation polymer drilling fluids

Low-permeability dense reservoirs,including micro-fractured reservoirs,are commonly characterized by high content of clay substances,high original water saturation,high sensitivity to invasive fluids,high capillary pressure,complicated structure and anisotropic,high flow-resistance and micro pore throats etc,.Generally they also have lots of natural micro fractures,probably leading to stress sensibility.Main damaging factors in such reservoirs are water-sensibility and water-blocking caused by invasive fluids during drilling and production operations.Once damaged,formation permeability can rarely recovered.Numerous studies have shown that damaging extent of water-blocking ranges from 70% to 90%.Main damaging mechanisms and influencing factors of water-blocking were systematically analyzed.Also some feasible precaution or treating approaches of water-blocking were put forward.In a laboratory setting,a new multi-functional drilling fluid composed mainly of amphion polymer,sulfonation polymer,high effectively preventive water-blocking surfactants,ideal packing temporary bridging agents(TBA) and film-forming agents,etc.,were developed.New low-damage drilling fluids has many advantages,such as good rheological properties,excellent effectiveness of water-blocking prevention,good temporary plugging effect,low filtration and ultra-low permeability(API filtration≤5 mL,HTHP filtration≤10 mL,mud cake frictional coefficient≤0.14,permeability recovery>81%),can efficiently prevent or minimize damage,preserve natural formation and enhance comprehensive development-investment effect in TUHA Jurassic dense sandstone reservoir formation with low-permeability,the only one developing integrated condense gas field.Some references can be provided to similar reservoir formations.

Protection of Environment from Damaged Nuclear Station and Transparent Inflatable Blanket for Cities—Protection from Radioactive Dust and Chemical, Biological Weapons

The author, in a series of previous articles, designed the “AB Dome” made of transparent thin film supported by a small additional air overpressure for the purpose of covering a city or other important large installations or sub-regions. In present article the author offers a variation in which a damaged nuclear station can be quickly covered by such a cheap inflatable dome. By containing the radioactive dust from the damaged nuclear station, the danger zone is reduced to about 2 km2 rather than large regions which requires the resettlement of huge masses of people and which stops indus-try in large areas. If there is a big city (as Tokyo) near the nuclear disaster or there is already a dangerous amount of radioactive dust near a city, the city may also be covered by a large inflatable transparent Dome. The building of a gi-gantic inflatable AB Dome over an empty flat surface is not difficult. The cover is spread on a flat surface and a venti-lator (fan system) pumps air under the film cover and lifts the new dome into place but inflation takes many hours. However, to cover a city, garden, forest or other obstacle course in contrast to an empty, mowed field, the thin film cannot be easily deployed over building or trees without risking damage to it by snagging and other complications. This article proposes a new method which solves this problem. The design is a double film blanket filled by light gas such as, methane, hydrogen, or helium - although of these, methane will be the most practical and least likely to leak. Sections of this AB Blanket are lighter than air and will rise in the atmosphere. They can be made on a flat area serving as an as-sembly area and delivered by dirigible or helicopter to station at altitude over the city. Here they connect to the already assembled AB Blanket subassemblies, cover the city in an AB Dome and protect it from bad weather, chemical, bio-logical and radioactive fallout or particulates. After assembly of the dome is completed, the light gas can be replaced by (heavier but cheaper) air. Two projects for Tokyo (Japan) and Moscow (Russia) are used in this paper for sample computation.

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

Emerging Trends in Damage Tolerance Assessment:A Review of Smart Materials and Self-Repairable Structures

The discipline of damage tolerance assessment has experienced significant advancements due to the emergence of smart materials and self-repairable structures.This review offers a comprehensive look into both traditional and innovative methodologies employed in damage tolerance assessment.After a detailed exploration of damage tolerance concepts and their historical progression,the review juxtaposes the proven techniques of damage assessment with the cutting-edge innovations brought about by smart materials and self-repairable structures.The subsequent sections delve into the synergistic integration of smart materials with self-repairable structures,marking a pivotal stride in damage tolerance by establishing an autonomous system for immediate damage identification and self-repair.This holistic approach broadens the applicability of these technologies across diverse sectors yet brings forth unique challenges demanding further innovation and research.Additionally,the review examines future prospects that combine advanced manufacturing processes with data-centric methodologies,amplifying the capabilities of these‘intelligent’structures.The review culminates by highlighting the transformative potential of this union between smart materials and self-repairable structures,promoting a sustainable and efficient engineering paradigm.

Damage response of conventionally reinforced two-way spanning concrete slab under eccentric impacting drop weight loading

Reinforced concrete(RC)structures are generally designed to carry quasi-static gravity loads through almost indispensable components namely slab,however,it may be subjected to high intense loads induced from the impact of projectiles generated by the tornado,falling construction equipment,and also from accidental explosions during their construction and service lifespan.Impacts due to rock/boulder falls do occur on the structures located especially in hilly areas.Such loadings are not predictable but may cause severe damage to the slab/structure.It stimulates structural engineers and researchers to investigate and understand the dynamic response of RC structures under such impulsive loading.This research work first investigates the performance of 1000×1000×75 mm^(3)conventionally reinforced two-way spanning normal strength concrete slab with only tension reinforcement(0.88%)under the concentric impact load(1035 N)using the finite element method based computer code,ABAQUS/Explicit-v.6.15.The impact load is delivered to the centroid of the slab using a solid-steel cylindroconical impactor(drop weight)with a flat nose of diameter 40 mm,having a total mass of 105 kg released from a fixed height of 2500 mm.Two popular concrete constitutive models in ABAQUS namely;Holmquist-Johnson-Cook(HJC)and Concrete Damage Plasticity(CDP),with strain rate effects as per fib MODEL CODE 2010,are used to model the concrete material behavior to impact loading and to simulate the damage to the slab.The slab response using these two models is analyzed and compared with the impact test results.The strain rate effect on the reinforcing steel bars has been incorporated in the analysis using the Malvar and Crawford(1998)approach.A classical elastoplastic kinematic idealization is considered to model the steel impactor and support system.Results reveal that the HJC model gives a little overestimation of peak displacement,maximum acceleration,and damage of the slab while the predictions given by the CDP model are in reasonable agreement with the experimental test results/observations available in the open literature.Following the validation of the numerical model,analyses have been extended to further investigate the damage response of the slab under eccentric impact loadings.In addition to the concentric location(P1)of the impacting device,five locations on a quarter of the slab i.e.,two along the diagonal(P2&P3),the other two along the mid-span(P4&P5),and the last one(P6)between P3 and P5,covering the entire slab,are considered.Computational results have been discussed and compared,and the evaluation of the most damaging location(s)of the impact is investigated.It has been found that the most critical location of the impact is not the centroid of the slab but the eccentric one with the eccentricity of 1/6th of the span from the centroid along the mid-span section.

Long Term Application of a Vehicle-Based Health Monitoring System to Short and Medium Span Bridges and Damage Detection Sensitivity

Largest portion of the bridge stock in almost any country and bridge owning organisation consists on ordinary bridges that has short or medium spans and are now deteriorating due to aging, etc. Therefore, it is becoming an important social concern to develop and put to practical use simple and efficient health monitoring systems for existing short and medium span (10 - 30 m) bridges. In this paper, one practical solution to the problem for condition assessment of short and medium span bridges was discussed. A vehicle-based measurement with a public bus as part of a public transit system (called “Bus monitoring system”) has been developed to be capable of detecting damage that may affect the structural safety of a bridge from long term vibration measurement data collected while the vehicle (bus) crossed the target bridges. This paper systematically describes how the system has been developed. The bus monitoring system aims to detect the transition from the damage acceleration period, in which the structural safety of an aged bridge declines sharply, to the deterioration period by continually monitoring the bridge of interest. To evaluate the practicality of the newly developed bus monitoring system, it has been field-tested over a period of about four years by using an in-service fixed-route bus operating on a bus route in the city of Ube, Yamaguchi Prefecture, Japan. The verification results thus obtained are also described in this paper. This study also evaluates the sensitivity of “characteristic deflection”, which is a bridge (health) condition indicator used by the bus monitoring system, in damage detection. Sensitivity of “characteristic deflection” is verified by introducing artificial damage into a bridge that has ended its service life and is awaiting removal. As the results, it will be able to make a rational long-term health monitoring system for existing short and mediumspan bridges, and then the system helps bridge administrators to establish the rational maintenance strategies.

Cholesterol and Sericin as First Aid for Damaged Cells

Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.

有限宽板孔边弹塑性变形测试

测量应变集中区域的弹塑性变形,对于研究材料损伤或微裂纹的产生,以预防宏观裂纹的产生及扩展具有重要的意义。为给航空发动机轮盘的损伤容限设计研究提供相关材料的力学实验参数,做了两个有限宽中心带孔试件的拉伸试验。试验中,采用单调逐级加、卸载的循环加载方式,并应用自动网格法和数字图像相关技术测量了孔周的全场位移分布。再应用最小二乘法将离散的位移分量拟合成二元多项式函数,求解出拉伸方向的应变分布,并给出孔边应力σ与孔边应变εy的关系曲线。

Formation damage mechanism and control strategy of the compound function of drilling fluid and fracturing fluid in shale reservoirs

For the analysis of the formation damage caused by the compound function of drilling fluid and fracturing fluid,the prediction method for dynamic invasion depth of drilling fluid is developed considering the fracture extension due to shale minerals erosion by oil-based drilling fluid.With the evaluation for the damage of natural and hydraulic fractures caused by mechanical properties weakening of shale fracture surface,fracture closure and rock powder blocking,the formation damage pattern is proposed with consideration of the compound effect of drilling fluid and fracturing fluid.The formation damage mechanism during drilling and completion process in shale reservoir is revealed,and the protection measures are raised.The drilling fluid can deeply invade into the shale formation through natural and induced fractures,erode shale minerals and weaken the mechanical properties of shale during the drilling process.In the process of hydraulic fracturing,the compound effect of drilling fluid and fracturing fluid further weakens the mechanical properties of shale,results in fracture closure and rock powder shedding,and thus induces stress-sensitive damage and solid blocking damage of natural/hydraulic fractures.The damage can yield significant conductivity decrease of fractures,and restrict the high and stable production of shale oil and gas wells.The measures of anti-collapse and anti-blocking to accelerate the drilling of reservoir section,forming chemical membrane to prevent the weakening of the mechanical properties of shale fracture surface,strengthening the plugging of shale fracture and reducing the invasion range of drilling fluid,optimizing fracturing fluid system to protect fracture conductivity are put forward for reservoir protection.

Implications of rare neurological disorders and perceptual errors in natural and synthetic consciousness

Recent theories on natural and synthetic consciousness overlook the geometric structure necessary for awareness of 3-dimensional space, as strikingly illustrated by left-neglect disorder. Furthermore, awareness of 3-dimensional space entails some surprisingly tenacious optical illusions, as demonstrated by an experiment in the text. Awareness of linear time is also crucial and complex. As a consequence, synthetic consciousness cannot be realized by simply intercomnecting a large number of electronic circuits constructed from ordinary chips and transistors. Since consciousness is a subjective experience, there is no sufficient condition for consciousness that can be experimentally confirmed. The most we can hope for is agreement on the necessary conditions for consciousness. Toward that end, this paper reviews some relevant clinical phenomena.

Micro Model of Carbon Fiber/Cyanate Ester Composites and Analysis of Machining Damage Mechanism

Machining damage occurs on the surface of carbon fiber reinforced polymer (CFRP) composites during processing. In the current simulation model of CFRP, the initial defects on the carbon fiber and the periodic random distribution of the reinforcement phase in the matrix are not considered in detail, which makes the characteristics of the cutting model significantly different from the actual processing conditions. In this paper, a novel three-phase model of carbon fiber/cyanate ester composites is proposed to simulate the machining damage of the composites. The periodic random distribution of the carbon fiber reinforced phase in the matrix was realized using a double perturbation algorithm. To achieve the stochastic distribution of the strength of a single carbon fiber, a novel method that combines the Weibull intensity distribution theory with the Monte Carlo method is presented. The mechanical properties of the cyanate matrix were characterized by fitting the stress-strain curves, and the cohesive zone model was employed to simulate the interface. Based on the model, the machining damage mechanism of the composites was revealed using finite element simulations and by conducting a theoretical analysis. Furthermore, the milling surfaces of the composites were observed using a scanning electron microscope, to verify the accuracy of the simulation results. In this study, the simulations and theoretical analysis of the carbon fiber/cyanate ester composite processing were carried out based on a novel three-phase model, which revealed the material failure and machining damage mechanism more accurately.

Transplantation of vascular endothelial growth factor-modified neural stem/progenitor cells promotes the recovery of neurological function following hypoxic-ischemic brain damage

Neural stem/progenitor cell （NSC） transplantation has been shown to effectively improve neurological function in rats with hypoxic-isch- emic brain damage. Vascular endothelial growth factor （VEGF） is a signaling protein that stimulates angiogenesis and improves neural regeneration. We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neo- natal rats. We produced and transfected a recombinant lentiviral vector containing the VEGF165gene into cultured NSCs. The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage. Compared with the NSCs group, VEGF mRNA and protein expression levels were increased in the transgene NSCs group, and learning and memory abilities were significantly improved at 30 days. Furthermore, histopathological changes were alleviated in these animals. Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function, and that its therapeutic effectiveness is better than that of unmodified NSCs.

A review of reservoir damage during hydraulic fracturing of deep and ultra-deep reservoirs

Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present unique challenges due to their deep burial depth(4500-8882 m),low matrix permeability,complex crustal stress conditions,high temperature and pressure(HTHP,150-200℃,105-155 MPa),coupled with high salinity of formation water.Consequently,the costs associated with their exploitation and development are exceptionally high.In deep and ultra-deep reservoirs,hydraulic fracturing is commonly used to achieve high and stable production.During hydraulic fracturing,a substantial volume of fluid is injected into the reservoir.However,statistical analysis reveals that the flowback rate is typically less than 30%,leaving the majority of the fluid trapped within the reservoir.Therefore,hydraulic fracturing in deep reservoirs not only enhances the reservoir permeability by creating artificial fractures but also damages reservoirs due to the fracturing fluids involved.The challenging“three-high”environment of a deep reservoir,characterized by high temperature,high pressure,and high salinity,exacerbates conventional forms of damage,including water sensitivity,retention of fracturing fluids,rock creep,and proppant breakage.In addition,specific damage mechanisms come into play,such as fracturing fluid decomposition at elevated temperatures and proppant diagenetic reactions at HTHP conditions.Presently,the foremost concern in deep oil and gas development lies in effectively assessing the damage inflicted on these reservoirs by hydraulic fracturing,comprehending the underlying mechanisms,and selecting appropriate solutions.It's noteworthy that the majority of existing studies on reservoir damage primarily focus on conventional reservoirs,with limited attention given to deep reservoirs and a lack of systematic summaries.In light of this,our approach entails initially summarizing the current knowledge pertaining to the types of fracturing fluids employed in deep and ultra-deep reservoirs.Subsequently,we delve into a systematic examination of the damage processes and mechanisms caused by fracturing fluids within the context of hydraulic fracturing in deep reservoirs,taking into account the unique reservoir characteristics of high temperature,high pressure,and high in-situ stress.In addition,we provide an overview of research progress related to high-temperature deep reservoir fracturing fluid and the damage of aqueous fracturing fluids to rock matrix,both artificial and natural fractures,and sand-packed fractures.We conclude by offering a summary of current research advancements and future directions,which hold significant potential for facilitating the efficient development of deep oil and gas reservoirs while effectively mitigating reservoir damage.

Exploring Ester Prodrugs: A Comprehensive Review of Approaches, Applications, and Methods

The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.

A methodology for damage evaluation of underground tunnels subjected to static loading using numerical modeling

We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensities.To account for these variations,we utilized a Monte Carlo Simulation(MCS)technique coupled with the finite difference code FLAC^(3D),to conduct two thousand seven hundred numerical simulations of a horseshoe tunnel located within a rock mass with different geological strength index system(GSIs)and subjected to different states of static loading.To quantify the severity of damage within the rock mass,we selected one stress-based(brittle shear ratio(BSR))and one strain-based failure criterion(plastic damage index(PDI)).Based on these criteria,we then developed fragility curves.Additionally,we used mathematical approximation techniques to produce vulnerability functions that relate the probabilities of various damage states to loading intensities for different quality classes of blocky rock mass.The results indicated that the fragility curves we obtained could accurately depict the evolution of the inner and outer shell damage around the tunnel.Therefore,we have provided engineers with a tool that can predict levels of damages associated with different failure mechanisms based on variations in rock mass quality and in situ stress state.Our method is a numerically developed,multi-variate approach that can aid engineers in making informed decisions about the robustness of underground tunnels.