The author puts forward the proposition of Complexity and Self Organized Criticality of Solid Earth System in the light of: (1) the science of complexity studies the mechanisms of emergence of complexity and is...The author puts forward the proposition of Complexity and Self Organized Criticality of Solid Earth System in the light of: (1) the science of complexity studies the mechanisms of emergence of complexity and is the science of the 21st century, (2) the study of complexity of the earth system would be one of the growing points occupying a strategic position in the development of geosciences in the 21st century. By the proposition we try to cogitate from a new viewpoint the ancient yet ever new solid earth system. The author abstracts the fundamental problem of the solid earth system from the essence of the generalized geological systems and processes which reads: the complexity and self organized criticality of the global nature, structure and dynamical behavior of the whole solid earth system emerging from the multiple coupling and superposition of non linear interactions among the multicomponents of the earths material and the multiple generalized geological (geological, geophysical, and geochemical) processes . Starting from this cognizance the author proposes eight major themes and the methodology of researches on the complexity and self organized criticality of the solid earth system.展开更多
The Jenkyns Event,more widely known as the Toarcian Oceanic Anoxic Event(T-OAE),is marked by globally distributed negative carbon-isotope excursions,widespread oxygen depletion,and large-scale organic carbon burial,wh...The Jenkyns Event,more widely known as the Toarcian Oceanic Anoxic Event(T-OAE),is marked by globally distributed negative carbon-isotope excursions,widespread oxygen depletion,and large-scale organic carbon burial,which indicate major climate/environmental perturbations in Earth's surface systems during the Early Jurassic.Although extensive research has been conducted in European continental settings,particularly in the western peri-Tethys regions,the impacts of this event beyond Europe remains largely unexplored.Here,a multiapproach study including investigations into the sporepollen assemblages,pyrite framboids,clay minerals,total organic carbon(TOC)levels,and organic carbon isotope(δ13Corg)levels in a lacustrine borehole section(MED1)from the Yin'gen-Ejinaqi Basin,North China,provides evidence of the occurrence of the Jenkyns Event and its extensive sedimentary responses in the eastern Tethys terrestrial systems.Two distinct spore-pollen assemblages have been identified in MED1(drilling depth:982.4 m to 1267.5 m),with the Cycadopites-Protopinus-Osmundacidites assemblage in the lower part(1267.5 m to 1132.9 m)indicating a middle Early Jurassic age and the Classopollis assemblage in the upper part(1132.9 m to 985.7 m)suggesting a Toarcian age.Framboidal pyrite data suggest more anoxic conditions during the deposition of black mudstone and shale intercalations in the lower part of the Classopollis assemblage(1132.9 m to 1066.9 m),which combined with organic carbon enrichment and negativeδ13Corg excursions,are considered the paleoenvironmental response to the Jenkyns Event in the study area.Furthermore,the evolution of vegetation groups changed from plant groups characterized by bisaccate and cycad pollen,as well as fern spores,to vegetation groups represented by Cheirolepidiaceae pollen across the Jenkyns Event,as evidenced by sporepollen data,together with the clay mineral assemblage change characterized by a notable increase in illite at the expense of kaolinite,suggests that while a subtropical-temperate climate persisted,a change toward warmer and drier conditions most likely occurred in the early Toarcian in the study area.In contrast to the humidification evidenced in many coastal settings,this aridification trend in the Yin'gen-Ejinaqi Basin aligns with the conditions in many inland areas.It is hypothesized that the underlying cause of these divergent changes may be linked to certain patterns of spatially variable water availability on land,potentially driven by extremified hydrological conditions.展开更多
Barshore is a small village in the Pishin District,Balochistan,Pakistan,with dry summers and cold rainy winters.This is an agrarian region,mostly with orchards of various fruit trees.This study investigated the physic...Barshore is a small village in the Pishin District,Balochistan,Pakistan,with dry summers and cold rainy winters.This is an agrarian region,mostly with orchards of various fruit trees.This study investigated the physico-chemical properties and macrofauna of soils under various agricultural management practices of this region.The concentrations of soil organic matter(SOM),soil organic carbon(SOC),nutrients,pH,electrical conductivity,soil texture,and the abundance and number of species of soil macrofauna of the agricultural fields were measured.Fifteen agricultural fields were sampled.Fourteen fields were orchards of apple,apricot or the mixture of apple and apricot trees and one field was a cropland,cultivated with wheat as a monocrop.The orchards were under conservation agricultural practices;whereas,the cropland was under conventional management.These agricultural lands were 2-26 years old.The concentration of soil organic matter(SOM)in the upper 0-10 cm depth of these field sites ranged from 11.6 g kg^(-1)to 32.8 g kg^(-1)soil.As compared to cropland,orchards had significantly higher concentration of SOM and SOC.A total of 18 soil macrofauna species were found and the most common and abundant were ants(Monomorium minimum,Camponotus pennsylvanicus,Solenopsis invicta,and Lasius niger)followed by Arion ssp.(Brown Slug)and earthworm Lumbricus terrestris.Regression analysis revealed non-significant relationship of the age and the concentration of SOM with the number of macrofauna species and with the concentrations of total mineral nitrogen,bioavailable phosphorus and clay.The existence of ants had no relationship with the concentration of SOM;whereas,existence of Lumbricus terrestris tended to had a positive relationship with the concentration of SOM.The field of tree-based intercropping system was 2 years of age since the land was converted from rangeland to a cropland,had two ant species coexisting.This indicates the positive influence of crop diversification on soil macrofauna.展开更多
Porous aromatic framework 1(PAF-1)is an extremely representative nanoporous organic framework owing to its high stability and exceptionally high surface area.Currently,the synthesis of PAF-1 is catalyzed by the Ni(COD...Porous aromatic framework 1(PAF-1)is an extremely representative nanoporous organic framework owing to its high stability and exceptionally high surface area.Currently,the synthesis of PAF-1 is catalyzed by the Ni(COD)2/COD/bpy system,suffering from great instability and high cost.Herein,we developed an in situ reduction of the Ni(II)catalytic system to synthesize PAF-1 in low cost and high yield.The active Ni(0)species produced from the NiCl_(2)/bpy/NaI/Mg catalyst system can effectively catalyze homocoupling of tetrakis(4-bromophenyl)methane at the room temperature to form PAF-1 with high Brunauer-Emmett-Teller(BET)-specific surface area up to 4948 m^(2) g^(−1)(Langmuir surface area,6785 m2 g−1).The possible halogen exchange and dehalogenation coupling mechanisms for this new catalytic process in PAF's synthesis are discussed in detail.The efficiency and universality of this innovative catalyst system have also been demonstrated in other PAFs'synthesis.This work provides a cheap,facile,and efficient method for scalable synthesis of PAFs and explores their application for high-pressure storage of Xe and Kr.展开更多
The development of various artificial electronics and machines would explosively increase the amount of information and data,which need to be processed via in-situ remediation.Bioinspired synapse devices can store and...The development of various artificial electronics and machines would explosively increase the amount of information and data,which need to be processed via in-situ remediation.Bioinspired synapse devices can store and process signals in a parallel way,thus improving fault tolerance and decreasing the power consumption of artificial systems.The organic field effect transistor(OFET)is a promising component for bioinspired neuromorphic systems because it is suitable for large-scale integrated circuits and flexible devices.In this review,the organic semiconductor materials,structures and fabrication,and different artificial sensory perception systems functions based on neuromorphic OFET devices are summarized.Subsequently,a summary and challenges of neuromorphic OFET devices are provided.This review presents a detailed introduction to the recent progress of neuromorphic OFET devices from semiconductor materials to perception systems,which would serve as a reference for the development of neuromorphic systems in future bioinspired electronics.展开更多
In-situ upgrading by heating is feasible for low-maturity shale oil,where the pore space dynamically evolves.We characterize this response for a heated substrate concurrently imaged by SEM.We systematically follow the...In-situ upgrading by heating is feasible for low-maturity shale oil,where the pore space dynamically evolves.We characterize this response for a heated substrate concurrently imaged by SEM.We systematically follow the evolution of pore quantity,size(length,width and cross-sectional area),orientation,shape(aspect ratio,roundness and solidity)and their anisotropy—interpreted by machine learning.Results indicate that heating generates new pores in both organic matter and inorganic minerals.However,the newly formed pores are smaller than the original pores and thus reduce average lengths and widths of the bedding-parallel pore system.Conversely,the average pore lengths and widths are increased in the bedding-perpendicular direction.Besides,heating increases the cross-sectional area of pores in low-maturity oil shales,where this growth tendency fluctuates at<300℃ but becomes steady at>300℃.In addition,the orientation and shape of the newly-formed heating-induced pores follow the habit of the original pores and follow the initial probability distributions of pore orientation and shape.Herein,limited anisotropy is detected in pore direction and shape,indicating similar modes of evolution both bedding-parallel and bedding-normal.We propose a straightforward but robust model to describe evolution of pore system in low-maturity oil shales during heating.展开更多
The existence and risk of emerging organic contaminants(EOCs)have been under consideration and paid much effort to degrade these pollutants.Fenton system is one of the most widely used technologies to solve this probl...The existence and risk of emerging organic contaminants(EOCs)have been under consideration and paid much effort to degrade these pollutants.Fenton system is one of the most widely used technologies to solve this problem.The original Fenton system relies on the hydroxyl radicals produced by Fe(Ⅱ)/H_(2)O_(2) to oxidize the organic contaminants.However,the application of the Fenton system is limited by its low iron cycling efficiency and the high risks of hydrogen peroxide transportation and storage.The introduction of external energy(including light and electricity etc.)can effectively promote the Fe(Ⅲ)/Fe(Ⅱ)cycle and the reduction of oxygen to produce hydrogen peroxide in situ.This review introduces three in-situ Fenton systems,which are electro-Fenton,Photo-Fenton,and chemical reaction.The mechanism,influencing factors,and catalysts of these three in-situ Fenton systems in degrading EOCs are discussed systematically.This review strengthens the understanding of Fenton and in-situ Fenton systems in degradation,offering further insight into the real application of the in-situ Fenton system in the removal of EOCs.展开更多
In this editorial we comment on the article by Kuwahara et al,published in the recent issue of the World Journal of Cardiology.In this interesting paper,the authors showed a correlation between portal vein pulsatility...In this editorial we comment on the article by Kuwahara et al,published in the recent issue of the World Journal of Cardiology.In this interesting paper,the authors showed a correlation between portal vein pulsatility ratio,examined by bedside ultrasonography,and prognosis of hospitalized patients with acute heart failure.Systemic congestion is being notoriously underdetected in the acutely ill population with conventional methods like clinical examination,biomarkers,central venous pressure estimation and X-rays.However,congestion should be a key therapeutic target due to its deleterious effects to end organ function and subsequently patient prognosis.Doppler flow assessment of the abdominal veins is gaining popularity worldwide,as a valuable tool in estimating comprehensively congestion and giving a further insight into hemodynamics and patient management.展开更多
Ploughing and fertilization practices in rice-wheat system have deteriorated the soil carbon (C) pools. Conservation agriculture (CA) based management approaches have proven to enhance C sequestration and reverse the ...Ploughing and fertilization practices in rice-wheat system have deteriorated the soil carbon (C) pools. Conservation agriculture (CA) based management approaches have proven to enhance C sequestration and reverse the loss of soil-organic-carbon (SOC), which further enhances soil fertility. Different fractions of SOC pools react to the alterations in management practices and indicate changes in SOC dynamics as compared to total C in the soil. Higher SOC levels in soil have been observed in case of reduced/no-till (NT) practices than conventional tillage (CT). However, between CT and zero tillage/NT, total SOC stocks diminished with an increase in soil depth, which demonstrated that the benefits of SOC are more pronounced in the topsoil under NT. Soil aggregation provides physical protection to C associated with different-sized particles, thus, the improvement in soil aggregation through CA is an effective way to mitigate soil C loss. Along with less soil disturbance, residual management, suitable crop rotation, rational application of manures and fertilizers, and integrated nutrient management have been found to be effective in not only improving soil C stock but also enhancing the soil health and productivity. Thus, CA can be considered as a potential method in the build-up of SOC of soil in rice-wheat system.展开更多
BACKGROUND Infants'nutrition significantly influences their growth,development,and overall well-being.With the increasing demand for organic infant formula driven by the perception of health benefits and growing a...BACKGROUND Infants'nutrition significantly influences their growth,development,and overall well-being.With the increasing demand for organic infant formula driven by the perception of health benefits and growing awareness of natural feeding options,it is crucial to conduct a comparative analysis of the gastrointestinal tolerability between organic and traditional infant formulas.AIM To provide a concise and precise analysis of the gastrointestinal tolerability of organic infant formula compared to traditional infant formula.Due to limited direct comparisons,the review synthesizes available literature on each formula type,presenting insights into their potential effects on infants'digestive health.METHODS An extensive literature search was conducted,compiling studies on organic and traditional infant formulas,their compositions,and reported effects on gastrointestinal tolerability.We searched academic databases such as PubMed and Google Scholar and specialized nutrition,paediatrics,and infant health journals using relevant keywords till October 1,2023.RESULTS Although specific comparative studies are scarce and formula heterogeneity is a significant limitation,this systematic review provides an in-depth understanding of organic infant formulas'composition and potential benefits.While scientific evidence directly comparing gastrointestinal tolerability is limited,organic formulas strive to use carefully selected organic ingredients to imitate breast milk composition.Potential benefits include improved lipid profiles,higher methionine content,and decreased antibiotic-resistant bacteria levels.Understanding the gastrointestinal tolerability of organic and traditional infant formulas is crucial for parents and healthcare providers to make informed decisions.CONCLUSION Despite limitations in direct comparisons,this systematic review provides insights into the composition and potential benefits of organic infant formulas.It emphasizes the need for further research to elucidate their gastrointestinal effects comprehensively.展开更多
Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their...Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. Mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t DM ha<sup>-1</sup>) and contributed the most total N (167 kg∙ha<sup>-1</sup>) and total C (3043 kg∙ha<sup>-1</sup>) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t DM ha<sup>-1</sup> with a total N yield of 319 kg N ha<sup>-1</sup> and total C production of 3835 kg C ha<sup>-1</sup>. The WSL treatments had only small effects on rye forage yield and N concentration, possibly due to mineralization of N from a large SOC pool already in place. The CSL treatments also had only minimal effects on sorghum-sudangrass forage production. Winter pea, arrow leaf and crimson clover were productive cool season legumes and could be useful as green manure crops. Mungbean and cowpea (Vigna unguiculata [L.] Walp.) were highly productive warm season legumes but may include more production risk in green manure systems due to soil moisture competition.展开更多
The developed auxiliary software serves to simplify, standardize and facilitate the software loading of the structural organization of a complex technological system, as well as its further manipulation within the pro...The developed auxiliary software serves to simplify, standardize and facilitate the software loading of the structural organization of a complex technological system, as well as its further manipulation within the process of solving the considered technological system. Its help can be especially useful in the case of a complex structural organization of a technological system with a large number of different functional elements grouped into several technological subsystems. This paper presents the results of its application for a special complex technological system related to the reference steam block for the combined production of heat and electricity.展开更多
Systemic lupus erythematosus(SLE)is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens,immune complex deposition,and chronic inflammation at classic target orga...Systemic lupus erythematosus(SLE)is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens,immune complex deposition,and chronic inflammation at classic target organs such as skin,joints,and kidneys.Despite substantial advances in the diagnosis and management of SLE,the burden of disease remains high.It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients.In most patients,constitutional,mucocutaneous,and musculoskeletal symptoms represent the earliest complaints;these symptoms can include fatigue,lupus-specific rash,mouth ulcers,alopecia,joint pain,and myalgia.In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria,which include a systematic evaluation of clinical manifestations(weighted within each domain)and autoantibody profiles(such as anti-double-stranded DNA,anti-Sm,hypocomplementaemia,or antiphospholipid antibodies).Nonpharmacotherapy management is tailored to the individual,with specific lifestyle interventions and patient education to improve quality of life and medication(such as hydroxychloroquine or immunosuppressant)adherence.展开更多
With the beginning of the information systems’ spreading, people started thinking about using them for making business decisions. Computer technology solutions, such as the Decision Support System, make the decision-...With the beginning of the information systems’ spreading, people started thinking about using them for making business decisions. Computer technology solutions, such as the Decision Support System, make the decision-making process less complex and simpler for problem-solving. In order to make a high-quality business decision, managers need to have a great deal of appropriate information. Nonetheless, this complicates the process of making appropriate decisions. In a situation like that, the possibility of using DSS is quite logical. The aim of this paper is to find out the intended use of DSS for medium and large business organizations in USA by applying the Technology Acceptance Model (TAM). Different models were developed in order to understand and predict the use of information systems, but the information systems community mostly used TAM to ensure this issue. The purpose of the research model is to determine the elements of analysis that contribute to these results. The sample for the research consisted of the target group that was supposed to have completed an online questionnaire about the manager’s use of DSS in medium and large American companies. The information obtained from the questionnaires was analyzed through the SPSS statistical software. The research has indicated that, this is primarily used due to a significant level of Perceived usefulness and For the Perceived ease of use.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
Mechanically durable transparent electrodes are essential for achieving long-term stability in flexible optoelectronic devices.Furthermore,they are crucial for applications in the fields of energy,display,healthcare,a...Mechanically durable transparent electrodes are essential for achieving long-term stability in flexible optoelectronic devices.Furthermore,they are crucial for applications in the fields of energy,display,healthcare,and soft robotics.Conducting meshes represent a promising alternative to traditional,brittle,metal oxide conductors due to their high electrical conductivity,optical transparency,and enhanced mechanical flexibility.In this paper,we present a simple method for fabricating an ultra-transparent conducting metal oxide mesh electrode using selfcracking-assisted templates.Using this method,we produced an electrode with ultra-transparency(97.39%),high conductance(Rs=21.24Ωsq^(−1)),elevated work function(5.16 eV),and good mechanical stability.We also evaluated the effectiveness of the fabricated electrodes by integrating them into organic photovoltaics,organic light-emitting diodes,and flexible transparent memristor devices for neuromorphic computing,resulting in exceptional device performance.In addition,the unique porous structure of the vanadium-doped indium zinc oxide mesh electrodes provided excellent flexibility,rendering them a promising option for application in flexible optoelectronics.展开更多
Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous tissue.They can lead to...Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous tissue.They can lead to severe nervous system dysfunction,eventually affecting multiple organs and systems.Several hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.展开更多
Over the centuries,the regeneration field has been puzzled by the dual response of the central nervous system(CNS-brain,spinal cord,cranial nervesⅠandⅡ)and the peripheral nervous system(PNS that refers to all the ne...Over the centuries,the regeneration field has been puzzled by the dual response of the central nervous system(CNS-brain,spinal cord,cranial nervesⅠandⅡ)and the peripheral nervous system(PNS that refers to all the nerves that innervate muscles,skin,organs,bones among others).Even Ramon y Cajal had noticed that an injury to the PNS often leads to axon regrowth,in contrast to the CNS.展开更多
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 functio...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.展开更多
The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and main...The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.展开更多
文摘The author puts forward the proposition of Complexity and Self Organized Criticality of Solid Earth System in the light of: (1) the science of complexity studies the mechanisms of emergence of complexity and is the science of the 21st century, (2) the study of complexity of the earth system would be one of the growing points occupying a strategic position in the development of geosciences in the 21st century. By the proposition we try to cogitate from a new viewpoint the ancient yet ever new solid earth system. The author abstracts the fundamental problem of the solid earth system from the essence of the generalized geological systems and processes which reads: the complexity and self organized criticality of the global nature, structure and dynamical behavior of the whole solid earth system emerging from the multiple coupling and superposition of non linear interactions among the multicomponents of the earths material and the multiple generalized geological (geological, geophysical, and geochemical) processes . Starting from this cognizance the author proposes eight major themes and the methodology of researches on the complexity and self organized criticality of the solid earth system.
基金financially supported by China Geological Survey Project(DD20230138DD20242504)+1 种基金The National Natural Science Foundation of China(Grant Numbers 41702366)The Sinopec Project(34550000-21FW2099-0055)。
文摘The Jenkyns Event,more widely known as the Toarcian Oceanic Anoxic Event(T-OAE),is marked by globally distributed negative carbon-isotope excursions,widespread oxygen depletion,and large-scale organic carbon burial,which indicate major climate/environmental perturbations in Earth's surface systems during the Early Jurassic.Although extensive research has been conducted in European continental settings,particularly in the western peri-Tethys regions,the impacts of this event beyond Europe remains largely unexplored.Here,a multiapproach study including investigations into the sporepollen assemblages,pyrite framboids,clay minerals,total organic carbon(TOC)levels,and organic carbon isotope(δ13Corg)levels in a lacustrine borehole section(MED1)from the Yin'gen-Ejinaqi Basin,North China,provides evidence of the occurrence of the Jenkyns Event and its extensive sedimentary responses in the eastern Tethys terrestrial systems.Two distinct spore-pollen assemblages have been identified in MED1(drilling depth:982.4 m to 1267.5 m),with the Cycadopites-Protopinus-Osmundacidites assemblage in the lower part(1267.5 m to 1132.9 m)indicating a middle Early Jurassic age and the Classopollis assemblage in the upper part(1132.9 m to 985.7 m)suggesting a Toarcian age.Framboidal pyrite data suggest more anoxic conditions during the deposition of black mudstone and shale intercalations in the lower part of the Classopollis assemblage(1132.9 m to 1066.9 m),which combined with organic carbon enrichment and negativeδ13Corg excursions,are considered the paleoenvironmental response to the Jenkyns Event in the study area.Furthermore,the evolution of vegetation groups changed from plant groups characterized by bisaccate and cycad pollen,as well as fern spores,to vegetation groups represented by Cheirolepidiaceae pollen across the Jenkyns Event,as evidenced by sporepollen data,together with the clay mineral assemblage change characterized by a notable increase in illite at the expense of kaolinite,suggests that while a subtropical-temperate climate persisted,a change toward warmer and drier conditions most likely occurred in the early Toarcian in the study area.In contrast to the humidification evidenced in many coastal settings,this aridification trend in the Yin'gen-Ejinaqi Basin aligns with the conditions in many inland areas.It is hypothesized that the underlying cause of these divergent changes may be linked to certain patterns of spatially variable water availability on land,potentially driven by extremified hydrological conditions.
基金We are grateful to the Department of Soil Science,Agricultural,Research Institute,Quetta,Pakistan for provision of laboratory facilities for chemical analysis of soil samples.We extend our gratitude to the Department of Zoology,University of Balochistan,Pakistan for the identification of soil fauna。
文摘Barshore is a small village in the Pishin District,Balochistan,Pakistan,with dry summers and cold rainy winters.This is an agrarian region,mostly with orchards of various fruit trees.This study investigated the physico-chemical properties and macrofauna of soils under various agricultural management practices of this region.The concentrations of soil organic matter(SOM),soil organic carbon(SOC),nutrients,pH,electrical conductivity,soil texture,and the abundance and number of species of soil macrofauna of the agricultural fields were measured.Fifteen agricultural fields were sampled.Fourteen fields were orchards of apple,apricot or the mixture of apple and apricot trees and one field was a cropland,cultivated with wheat as a monocrop.The orchards were under conservation agricultural practices;whereas,the cropland was under conventional management.These agricultural lands were 2-26 years old.The concentration of soil organic matter(SOM)in the upper 0-10 cm depth of these field sites ranged from 11.6 g kg^(-1)to 32.8 g kg^(-1)soil.As compared to cropland,orchards had significantly higher concentration of SOM and SOC.A total of 18 soil macrofauna species were found and the most common and abundant were ants(Monomorium minimum,Camponotus pennsylvanicus,Solenopsis invicta,and Lasius niger)followed by Arion ssp.(Brown Slug)and earthworm Lumbricus terrestris.Regression analysis revealed non-significant relationship of the age and the concentration of SOM with the number of macrofauna species and with the concentrations of total mineral nitrogen,bioavailable phosphorus and clay.The existence of ants had no relationship with the concentration of SOM;whereas,existence of Lumbricus terrestris tended to had a positive relationship with the concentration of SOM.The field of tree-based intercropping system was 2 years of age since the land was converted from rangeland to a cropland,had two ant species coexisting.This indicates the positive influence of crop diversification on soil macrofauna.
基金National Natural Science Foundation of China,Grant/Award Numbers:21975096,22178280Key Laboratory of Nuclear Data Foundation,Grant/Award Number:JCKY2021201C151Young Talent Support Plan,Grant/Award Number:HG6J001。
文摘Porous aromatic framework 1(PAF-1)is an extremely representative nanoporous organic framework owing to its high stability and exceptionally high surface area.Currently,the synthesis of PAF-1 is catalyzed by the Ni(COD)2/COD/bpy system,suffering from great instability and high cost.Herein,we developed an in situ reduction of the Ni(II)catalytic system to synthesize PAF-1 in low cost and high yield.The active Ni(0)species produced from the NiCl_(2)/bpy/NaI/Mg catalyst system can effectively catalyze homocoupling of tetrakis(4-bromophenyl)methane at the room temperature to form PAF-1 with high Brunauer-Emmett-Teller(BET)-specific surface area up to 4948 m^(2) g^(−1)(Langmuir surface area,6785 m2 g−1).The possible halogen exchange and dehalogenation coupling mechanisms for this new catalytic process in PAF's synthesis are discussed in detail.The efficiency and universality of this innovative catalyst system have also been demonstrated in other PAFs'synthesis.This work provides a cheap,facile,and efficient method for scalable synthesis of PAFs and explores their application for high-pressure storage of Xe and Kr.
基金the National Natural Science Foundation of China(U21A20497)Singapore National Research Foundation Investigatorship(Grant No.NRF-NRFI08-2022-0009)。
文摘The development of various artificial electronics and machines would explosively increase the amount of information and data,which need to be processed via in-situ remediation.Bioinspired synapse devices can store and process signals in a parallel way,thus improving fault tolerance and decreasing the power consumption of artificial systems.The organic field effect transistor(OFET)is a promising component for bioinspired neuromorphic systems because it is suitable for large-scale integrated circuits and flexible devices.In this review,the organic semiconductor materials,structures and fabrication,and different artificial sensory perception systems functions based on neuromorphic OFET devices are summarized.Subsequently,a summary and challenges of neuromorphic OFET devices are provided.This review presents a detailed introduction to the recent progress of neuromorphic OFET devices from semiconductor materials to perception systems,which would serve as a reference for the development of neuromorphic systems in future bioinspired electronics.
基金financially supported by the National Key Research and Development Program of China(Grant No.2022YFE0129800)the National Natural Science Foundation of China(Grant No.42202204)。
文摘In-situ upgrading by heating is feasible for low-maturity shale oil,where the pore space dynamically evolves.We characterize this response for a heated substrate concurrently imaged by SEM.We systematically follow the evolution of pore quantity,size(length,width and cross-sectional area),orientation,shape(aspect ratio,roundness and solidity)and their anisotropy—interpreted by machine learning.Results indicate that heating generates new pores in both organic matter and inorganic minerals.However,the newly formed pores are smaller than the original pores and thus reduce average lengths and widths of the bedding-parallel pore system.Conversely,the average pore lengths and widths are increased in the bedding-perpendicular direction.Besides,heating increases the cross-sectional area of pores in low-maturity oil shales,where this growth tendency fluctuates at<300℃ but becomes steady at>300℃.In addition,the orientation and shape of the newly-formed heating-induced pores follow the habit of the original pores and follow the initial probability distributions of pore orientation and shape.Herein,limited anisotropy is detected in pore direction and shape,indicating similar modes of evolution both bedding-parallel and bedding-normal.We propose a straightforward but robust model to describe evolution of pore system in low-maturity oil shales during heating.
基金supported by the National Natural Science Foundation of China(No.21906056No.22176060)+2 种基金the Undergraduate Training Program on Innovation and Entrepreneurship(S202110251087)the Science and Technology Commission of Shanghai Municipality(22ZR1418600)Shanghai Municipal Science and Technology(No.20DZ2250400).
文摘The existence and risk of emerging organic contaminants(EOCs)have been under consideration and paid much effort to degrade these pollutants.Fenton system is one of the most widely used technologies to solve this problem.The original Fenton system relies on the hydroxyl radicals produced by Fe(Ⅱ)/H_(2)O_(2) to oxidize the organic contaminants.However,the application of the Fenton system is limited by its low iron cycling efficiency and the high risks of hydrogen peroxide transportation and storage.The introduction of external energy(including light and electricity etc.)can effectively promote the Fe(Ⅲ)/Fe(Ⅱ)cycle and the reduction of oxygen to produce hydrogen peroxide in situ.This review introduces three in-situ Fenton systems,which are electro-Fenton,Photo-Fenton,and chemical reaction.The mechanism,influencing factors,and catalysts of these three in-situ Fenton systems in degrading EOCs are discussed systematically.This review strengthens the understanding of Fenton and in-situ Fenton systems in degradation,offering further insight into the real application of the in-situ Fenton system in the removal of EOCs.
文摘In this editorial we comment on the article by Kuwahara et al,published in the recent issue of the World Journal of Cardiology.In this interesting paper,the authors showed a correlation between portal vein pulsatility ratio,examined by bedside ultrasonography,and prognosis of hospitalized patients with acute heart failure.Systemic congestion is being notoriously underdetected in the acutely ill population with conventional methods like clinical examination,biomarkers,central venous pressure estimation and X-rays.However,congestion should be a key therapeutic target due to its deleterious effects to end organ function and subsequently patient prognosis.Doppler flow assessment of the abdominal veins is gaining popularity worldwide,as a valuable tool in estimating comprehensively congestion and giving a further insight into hemodynamics and patient management.
文摘Ploughing and fertilization practices in rice-wheat system have deteriorated the soil carbon (C) pools. Conservation agriculture (CA) based management approaches have proven to enhance C sequestration and reverse the loss of soil-organic-carbon (SOC), which further enhances soil fertility. Different fractions of SOC pools react to the alterations in management practices and indicate changes in SOC dynamics as compared to total C in the soil. Higher SOC levels in soil have been observed in case of reduced/no-till (NT) practices than conventional tillage (CT). However, between CT and zero tillage/NT, total SOC stocks diminished with an increase in soil depth, which demonstrated that the benefits of SOC are more pronounced in the topsoil under NT. Soil aggregation provides physical protection to C associated with different-sized particles, thus, the improvement in soil aggregation through CA is an effective way to mitigate soil C loss. Along with less soil disturbance, residual management, suitable crop rotation, rational application of manures and fertilizers, and integrated nutrient management have been found to be effective in not only improving soil C stock but also enhancing the soil health and productivity. Thus, CA can be considered as a potential method in the build-up of SOC of soil in rice-wheat system.
文摘BACKGROUND Infants'nutrition significantly influences their growth,development,and overall well-being.With the increasing demand for organic infant formula driven by the perception of health benefits and growing awareness of natural feeding options,it is crucial to conduct a comparative analysis of the gastrointestinal tolerability between organic and traditional infant formulas.AIM To provide a concise and precise analysis of the gastrointestinal tolerability of organic infant formula compared to traditional infant formula.Due to limited direct comparisons,the review synthesizes available literature on each formula type,presenting insights into their potential effects on infants'digestive health.METHODS An extensive literature search was conducted,compiling studies on organic and traditional infant formulas,their compositions,and reported effects on gastrointestinal tolerability.We searched academic databases such as PubMed and Google Scholar and specialized nutrition,paediatrics,and infant health journals using relevant keywords till October 1,2023.RESULTS Although specific comparative studies are scarce and formula heterogeneity is a significant limitation,this systematic review provides an in-depth understanding of organic infant formulas'composition and potential benefits.While scientific evidence directly comparing gastrointestinal tolerability is limited,organic formulas strive to use carefully selected organic ingredients to imitate breast milk composition.Potential benefits include improved lipid profiles,higher methionine content,and decreased antibiotic-resistant bacteria levels.Understanding the gastrointestinal tolerability of organic and traditional infant formulas is crucial for parents and healthcare providers to make informed decisions.CONCLUSION Despite limitations in direct comparisons,this systematic review provides insights into the composition and potential benefits of organic infant formulas.It emphasizes the need for further research to elucidate their gastrointestinal effects comprehensively.
文摘Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. Mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t DM ha<sup>-1</sup>) and contributed the most total N (167 kg∙ha<sup>-1</sup>) and total C (3043 kg∙ha<sup>-1</sup>) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t DM ha<sup>-1</sup> with a total N yield of 319 kg N ha<sup>-1</sup> and total C production of 3835 kg C ha<sup>-1</sup>. The WSL treatments had only small effects on rye forage yield and N concentration, possibly due to mineralization of N from a large SOC pool already in place. The CSL treatments also had only minimal effects on sorghum-sudangrass forage production. Winter pea, arrow leaf and crimson clover were productive cool season legumes and could be useful as green manure crops. Mungbean and cowpea (Vigna unguiculata [L.] Walp.) were highly productive warm season legumes but may include more production risk in green manure systems due to soil moisture competition.
文摘The developed auxiliary software serves to simplify, standardize and facilitate the software loading of the structural organization of a complex technological system, as well as its further manipulation within the process of solving the considered technological system. Its help can be especially useful in the case of a complex structural organization of a technological system with a large number of different functional elements grouped into several technological subsystems. This paper presents the results of its application for a special complex technological system related to the reference steam block for the combined production of heat and electricity.
文摘Systemic lupus erythematosus(SLE)is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens,immune complex deposition,and chronic inflammation at classic target organs such as skin,joints,and kidneys.Despite substantial advances in the diagnosis and management of SLE,the burden of disease remains high.It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients.In most patients,constitutional,mucocutaneous,and musculoskeletal symptoms represent the earliest complaints;these symptoms can include fatigue,lupus-specific rash,mouth ulcers,alopecia,joint pain,and myalgia.In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria,which include a systematic evaluation of clinical manifestations(weighted within each domain)and autoantibody profiles(such as anti-double-stranded DNA,anti-Sm,hypocomplementaemia,or antiphospholipid antibodies).Nonpharmacotherapy management is tailored to the individual,with specific lifestyle interventions and patient education to improve quality of life and medication(such as hydroxychloroquine or immunosuppressant)adherence.
文摘With the beginning of the information systems’ spreading, people started thinking about using them for making business decisions. Computer technology solutions, such as the Decision Support System, make the decision-making process less complex and simpler for problem-solving. In order to make a high-quality business decision, managers need to have a great deal of appropriate information. Nonetheless, this complicates the process of making appropriate decisions. In a situation like that, the possibility of using DSS is quite logical. The aim of this paper is to find out the intended use of DSS for medium and large business organizations in USA by applying the Technology Acceptance Model (TAM). Different models were developed in order to understand and predict the use of information systems, but the information systems community mostly used TAM to ensure this issue. The purpose of the research model is to determine the elements of analysis that contribute to these results. The sample for the research consisted of the target group that was supposed to have completed an online questionnaire about the manager’s use of DSS in medium and large American companies. The information obtained from the questionnaires was analyzed through the SPSS statistical software. The research has indicated that, this is primarily used due to a significant level of Perceived usefulness and For the Perceived ease of use.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
基金supported by a National Research Foundation of Korea(NRF)grant(No.2016R1A3B 1908249)funded by the Korean government.
文摘Mechanically durable transparent electrodes are essential for achieving long-term stability in flexible optoelectronic devices.Furthermore,they are crucial for applications in the fields of energy,display,healthcare,and soft robotics.Conducting meshes represent a promising alternative to traditional,brittle,metal oxide conductors due to their high electrical conductivity,optical transparency,and enhanced mechanical flexibility.In this paper,we present a simple method for fabricating an ultra-transparent conducting metal oxide mesh electrode using selfcracking-assisted templates.Using this method,we produced an electrode with ultra-transparency(97.39%),high conductance(Rs=21.24Ωsq^(−1)),elevated work function(5.16 eV),and good mechanical stability.We also evaluated the effectiveness of the fabricated electrodes by integrating them into organic photovoltaics,organic light-emitting diodes,and flexible transparent memristor devices for neuromorphic computing,resulting in exceptional device performance.In addition,the unique porous structure of the vanadium-doped indium zinc oxide mesh electrodes provided excellent flexibility,rendering them a promising option for application in flexible optoelectronics.
基金supported by Fundacja ORLEN(donation No.161/XI/2022)(to GW).
文摘Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous tissue.They can lead to severe nervous system dysfunction,eventually affecting multiple organs and systems.Several hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.
基金supported by ANR(ANR-21-CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23-CE52-0007)+2 种基金UNADEV(A22018CS)UNADEV(A22020CS)(to SB)ERC(ERC-St17-759089)(to HN)。
文摘Over the centuries,the regeneration field has been puzzled by the dual response of the central nervous system(CNS-brain,spinal cord,cranial nervesⅠandⅡ)and the peripheral nervous system(PNS that refers to all the nerves that innervate muscles,skin,organs,bones among others).Even Ramon y Cajal had noticed that an injury to the PNS often leads to axon regrowth,in contrast to the CNS.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘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.
基金supported by the German Research Foundation(Deutsche Forschungsgemeinschaft)(DFG),project number 422179811 to RR and RA 689/12-1 to GR.
文摘The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.