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.

Task Coordination Organization Model and the Task Allocation Algorithm for Resource Contention of the Syncretic System

At present, robot embedded systems have some common problems such as closure and poor dynamic evolution. Aiming at resolving this situation, our paper focuses on improvements to the robot embedded system and sets up a new robot system architecture, and we propose a syncretic mechanism of a robot and SoftMan （SM）. In the syncretic system, the structural organization of the SoftMan group and its modes are particularly important in establishing the task coordination mechanism. This paper, therefore, proposes a coordination organization model based on the SoftMan group, and studies in detail the process of task allocation for resource contention, which facilitates a rational allocation of system resources. During our research, we introduced Resource Requirement Length Algorithm （RRLA） to calculate the resource requirements of the task and a resource conformity degree allocation algorithm of Resource Conformity Degree Algorithm （RCDA） for resource contention. Finally, a comparative evaluation of RCDA with five other frequently used task allocation algorithms shows that RCDA has higher success and accuracy rates with good stability and reliability.

Verify the Function of a Potential Growth-Regulating Gene in Marine Bivalve Using a Candidate Model Organism Mulinia lateralis

A better understanding of genetic bases of growth regulation is essential for bivalve breeding,which is helpful to improve the yield of the commercially important bivalves.While previous studies have identified some candidate genes accounting for variation in growth-related traits through genotype-phenotype association analyses,seldom of them have verified the functions of these putative,growth-related genes beyond the genomic level due to the difficulty of culturing commercial bivalves under laboratory conditions.Fortunately,dwarf surf clam Mulinia lateralis can serve as a model organism for studying marine bivalves given its short generation time,the feasibility of being grown under experimental conditions and the availability of genetic and biological information.Using dwarf surf clam as a model bivalve,we characterize E2F3,a gene that has been found to account for variation in growth in scallops by a previous genome-wide association study,and verify its function in growth regulation through RNA interference(RNAi)experiments.For the first time,E2F3 in dwarf surf clam,which is termed as MulE2F3,is characterized.The results reveal that dwarf surf clams with MulE2F3 knocked down exhibit a reduction in both shell size and soft-tissue weight,indicating the functions of MulE2F3 in positively regulating bivalve growth.More importantly,we demonstrate how dwarf surf clam can be used as a model organism to investigate gene functions in commercial bivalves,shedding light on genetic causes for variation in growth to enhance the efficiency of bivalve farming.

Research proceedings on amphibian model organisms

Model organisms have long been important in biology and medicine due to their specific characteristics. Amphibians, especially Xenopus, play key roles in answering fundamental questions on developmental biology, regeneration, genetics, and toxicology due to their large and abundant eggs, as well as their versatile embryos, which can be readily manipulated and developed in vivo. Furthermore, amphibians have also proven to be of considerable benefit in human disease research due to their conserved cellular developmental and genomic organization. This review gives a brief introduction on the progress and limitations of these animal models in biology and human disease research, and discusses the potential and challenge of Microhyla fissipes as a new model organism.

Experimental and modeling study of kinetics for methane hydrate formation in a crude oil-in-water emulsion

A low-viscosity emulsion of crude oil in water can be believed to be the bulk of a flow regime in a pipeline.To differentiate which crude oil would and which would not counter the blockage of flow due to gas hydrate formation in flow channels,varying amount of crude oil in water emulsion without any other extraneous additives has undergone methane gas hydrate formation in an autoclave cell.Crude oil was able to thermodynamically inhibit the gas hydrate formation as observed from its hydrate stability zone.The normalized rate of hydrate formation in the emulsion has been calculated from an illustrative chemical affinity model,which showed a decrease in the methane consumption（decreased normalized rate constant） with an increase in the oil content in the emulsion.Fourier transform infrared spectroscopy（FTIR） of the emulsion and characteristic properties of the crude oil have been used to find the chemical component that could be pivotal in selfinhibitory characteristic of the crude oil collected from Ankleshwar,India,against a situation of clogged flow due to formation of gas hydrate and establish flow assurance.

AN ADSORB MODEL OF ORGANIC ACID ON BASIC ZEOLITE NAX

The adsorb model of formic acid on NaX derived from TPD was discussed. It was showed that the adsorb sites were various exposed framework O2- centers bearing different basic intensity and spatial resistance. The h-peak was attributed to O2- near S-III in supercage and l-peak to O2- near S-II in beta-cage of faujusite zeolite. The model can explain the experimental results. Meanwhile, a relative standard of basic intensity based on TPD of formic acid was founded.

Application of Caenorhabditis elegans in screening active ingredients of traditional Chinese medicine

People continue to recognize the important role of Chinese medicine in the treatment of diseases,and there is an urgent need to clarify the mechanism of Chinese medicine.Because of the multi-target and multi-component characteristics of traditional Chinese medicine,it is difficult to elaborate from a single perspective.As a high-quality animal model,Caenorhabditis elegans with the characteristics of small size and fast reproduction,has been widely used in traditional Chinese medicine activity experiments.In this article,Caenorhabditis elegans,as model organisms used to screen the active components of traditional Chinese medicine were reviewed.

Analysis and Related Suggestions on the Whole Process Engineering Consulting Service Mode at Home and Abroad

This paper first introduces the basic connotation of China’s whole-process engineering consulting.Immediately,analyze the organization model,service procurement model and charging standards of foreign whole-process engineering consulting(international terminology full-life cycle engineering consultant).Second,discuss the government’s role in the development of engineering consulting from two aspects:service management and market access.Finally,combined with the above analysis,the specific problems faced in the implementation process of the whole process engineering consulting are compared.Provide relevant suggestions on how companies and individuals respond to industry development trends.

Long-term organic and inorganic fertilizations enhanced basic soil productivity in a fluvo-aquic soil

The improvement of soil productivity depends on a rational input of water and nutrients, optimal field management, and the increase of basic soil productivity（BSP）. In this study, BSP is defined as the productive capacity of a farmland soil with its own physical and chemical properties for a specific crop season under local field management. Based on 19-yr data of the long-term agronomic experiments（1989–2008） on a fluvo-aquic soil in Zhengzhou, Henan Province, China, the decision support system for agrotechnology transfer（DSSAT ver. 4.0） crop growth model was used to simulate yields by BSP of winter wheat（Triticum aestivium L.） and summer maize（Zea mays L.） to examine the relationship between BSP and soil organic carbon（SOC） under long-term fertilization. Five treatments were included：（1） no fertilization（control）,（2） nitrogen, phosphorus and potassium fertilizers（NPK）,（3） NPK plus manure（NPKM）,（4） 1.5 times of NPKM（1.5NPKM）, and（5） NPK plus straw（NPKS）. After 19 yr of treatments, the SOC stock increased 16.7, 44.2, 69.9, and 25.2% under the NPK, NPKM, 1.5NPKM, and NPKS, respectively, compared to the initial value. Among various nutrient factors affecting contribution percentage of BSP to winter wheat and summer maize, SOC was a major affecting factor for BSP in the fluvo-aquic soil. There were significant positive correlations between SOC stock and yields by BSP of winter wheat and summer maize（P〈0.01）, and yields by BSP of winter wheat and summer maize increased 154 and 132 kg ha^（–1） when SOC stock increased 1 t C ha^（–1）. Thus, increased SOC accumulation is a crucial way for increasing BSP in fluvo-aquic soil. The manure or straw combined application with chemical fertilizers significantly enhanced BSP compared to the application of chemical fertilizers alone.

A spatial multi-scale integer coding method and its application to three-dimensional model organization

With the rapid development of digital earth,smart city,and digital twin technology,the demands of three-dimensional model data’s application is getting higher and higher.These data tend to be multi-objectification,multi-type,multi-scale,complex spatial relationship,and large amount,which brings great challenges to the efficient organization of them.This paper mainly studies the organization of three-dimensional model data,and the main contributions are as follows:1)A integer coding method of three dimensional multi-scale grid is proposed,which can reduce the four-dimensional(spatial dimension and scale dimension)space into one-dimensional,and has better space and scale clustering characteristics by comparing with various types of grid coding.2)The binary algebra calculation method is proposed to realize the basic spatial relationship calculation of three-dimensional grid,which has higher spatial relationship computing ability than 3D-Geohash method;3)The multi-scale integer coding method is applied to the data organization of three-dimensional city model,and the experiment results show that:it is more efficient and stable than the threedimensional R-tree index and Geohash coding method in the establishment of index and the query of three dimensional space.

Utilization of 3D printing technology in hepatopancreatobiliary surgery

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Initiation of Setaria as a model plant

Model organisms such as Arabidopsis(Arabidopsis thaliana)and rice(Oryza sativa)have proven essential for efficient scientific discovery and development of new methods.With the diversity of plant lineages,some important processes such as C4 photosynthesis are not found in either Arabidopsis or rice,so new model species are needed.Due to their small diploid genomes,short life cycles,self-pollination,small adult statures and prolific seed production,domesticated foxtail millet(Setaria italica)and its wild ancestor,green foxtail(S.viridis),have recently been proposed as novel model species for functional genomics of the Panicoideae,especially for study of C4 photosynthesis.This review outlines the development of these species as model organisms,and discusses current challenges and future potential of a Setaria model.

dbDEMC 3.0:Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

MicroRNAs(miRNAs)are important regulators in gene expression.The dysregulation of miRNA expression is widely reported in the transformation from physiological to pathological states of cells.A large number of differentially expressed miRNAs(DEMs)have been identified in various human cancers by using high-throughput technologies,such as microarray and miRNAseq.Through mining of published studies with high-throughput experiment information,the database of DEMs in human cancers(dbDEMC)was constructed with the aim of providing a systematic resource for the storage and query of the DEMs.Here we report an update of the dbDEMC to version 3.0,which contains two-fold more data entries than the second version and now includes also data from mice and rats.The dbDEMC 3.0 contains 3268 unique DEMs in 40 different cancer types.The current datasets for differential expression analysis have expanded to 9 generalized categories.Moreover,the current release integrates functional annotations of DEMs obtained by using experimentally validated targets.The annotations can be of great benefit to the intensive analysis of the roles of DEMs in cancer.In summary,dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers.The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.

Sedimentary environment and model for lacustrine organic matter enrichment:lacustrine shale of the Early Jurassic Da’anzhai Formation,central Sichuan Basin,China

Based on the analysis of element geochemistry and total organic carbon(TOC),this study investigates the main factors controlling organic matter(OM)enrichment,reconstructs the evolution process of the sedimentary environment,and proposes a dynamic OM enrichment model of the Jurassic Da’anzhai(D)Formation,Sichuan Basin.The results indicate that the Sichuan Basin was generally dominated by a warm and oxidizing sedimentary environment,but with some peculiarities,such as a hotter climate in the D1 member and more anoxic lake water in the D2a member.The sedimentary evolution of the Da’anzhai Formation can be divided into a fluctuating sedimentary stage,a stable sedimentary stage and a reef-building stage.The D2a member showed the strongest hypoxia,the weakest weathering,the largest amount of terrestrial inputs,and the highest TOC content.The TOC is positively correlated with reducing conditions and terrestrial inputs,negatively correlated with weathering.Based on these findings,it is suggested that the global climate in the Early Jurassic period had a complex regional effect and the global oceanic anoxic events of the Toarcian did not spread to the Sichuan Basin.Thus,the anoxic deep water,high terrestrial inputs,and weak weathering were conducive to rapid deposition and preservation of lacustrine OM.

Regeneration across Metazoan Phylogeny:Lessons from Model Organisms

Comprehending the diversity of the regenerative potential across metazoan phylogeny represents a fundamental challenge in biology. Invertebrates like Hydra and planarians exhibit amazing feats of regeneration, in which an entire organism can be restored t^om minute body segments. Vertebrates like teleost fish and amphibians can also regrow large sections of the body. While this regenerative capacity is greatly attenuated in mammals, there are portions of major organs that remain regenerative. Regardless of the extent, there are common basic strategies to regeneration, including activation of adult stem cells and proliferation of differentiated cells. Here, we discuss the cellular features and molecular mechanisms that are involved in regeneration in different model organisms, including 14ydra, planarians, zebrafish and newts as well as in several mammalian organs.

Azolla-A Model Organism for Plant Genomic Studies

The aquatic ferns of the genus Azolla are nitrogen-fixing plants that have great potentials in agricultural production and environmental conservation. Azolla in many aspects is qualified to serve as a model organism for genomic studies because of its importance in agriculture, its unique position in plant evolution, its symbiotic relationship with the N2-fixing cyanobacterium, Anabaena azollae, and its moderate-sized genome. The goals of this genome project are not only to understand the biology of the Azolla genome to promote its applications in biological research and agriculture practice but also to gain critical insights about evolution of plant genomes. Together with the strategic and technical improvement as well as cost reduction of DNA sequencing, the deciphering of their genetic code is imminent.

WRF/CHEM modeling of impacts of weather conditions modified by urban expansion on secondary organic aerosol formation over Pearl River Delta

In this paper, the online Weather Research and Forecasting and Chemistry （WRF/CHEM） model, coupled with urban canopy （UCM） and biogenic-emission models, is used to explore impacts of urban expansion on secondary organic aerosols （SOA） formation. Two scenarios of urban maps are used in WRF/CHEM to represent early 1990s （pre-urbanization） and current urban distribution in the Pearl River Delta （PRD）. Month-long simulation results using the above land-use scenarios for March 2001 show： （1） urbanization can increase monthly averaged temperatures by about 0.63 ℃, decrease monthly averaged 10-m wind speeds by 38%, increase monthly averaged boundary-layer depths by 80 m, and decrease monthly aver- aged water mixing ratio by 0.2g/kg. （2） Changes in meteorological conditions can result in detectable concentration changes of NOx, VOC, O3 and NO3 radicals. Urbanization decreases surface NOx and VOC concentrations by a maximum of 4 ppbv and 1.5 ppbv, respectively. Surface O3 and NO3 radical concentrations over major cities increase by about 2-4 ppbv and 4-12 pptv, respectively; areas with increasing O3 and NO3 radical concentrations generally coincide with the areas of temperature increase and wind speed reduction where NOx and VOC decrease. （3） Urbanization can induce 9% increase of SOA in Foshan, Zhongshan and west Guangzhou and 3% decrease in Shenzhen and Dongguan. Over PRD major cities, SOA from Aitken mode reduces by 30% but with more than 70% SOA from accumulate mode. Urbanization has stronger influence on SOA formation from Aitken mode. （4） Over the PRD, 55-65% SOA comes from aromatics precursors. Urbanization has strongest influence on aromatics precursors to produce SOA （14% increase）, while there is less influence on alkane precursors. Alkene precursors have negative contribution to SOA formation under urbanization situation.

Bumblebees with the socially transmitted microbiome:A novel model organism for gut microbiota research

Eusocial bumble and honey bees are important pollinators for global ecology and the agricultural economy.Although both the bumble and honey bees possess similar and host-restricted gut microbiota,they differ in aspects of morphology,autonomy,physiology,behavior,and life cycle.The social bee gut bacteria exhibit host specificity that is likely a result of long-term co-evolution.The unique life cycle of bumblebees is key for the acquisition and development of their gut microbiota,and affects the strain-level diversity of the core bacterial species.Studies on bumblebee gut bacteria show that they retain less functional capacity for carbohydrate metabolism compared with that of the honeybee.We discuss the potential roles of the bumblebee gut microbiota against pathogenic threats and the application of host-specific probiotics for bumblebees.Given the advantages of the bumblebee microbiome,including the simple structure and host specificity,and the ease of manipulating bumblebee colonies,we propose that bumblebees may provide a valuable system for understanding the general principles of host-microbe interactions,gut-brain axis,and vertical transmission.

Three-dimensional organ modeling based on deformable surfaces applied to radio-oncology

This paper describes a method based on an energy minimizing deformable model applied to the 3D biomechanical modeling of a set of organs considered as regions of interest (ROI) for radiotherapy. The initial model consists of a quadratic surface that is deformed to the exact contour of the ROI by means of the physical properties of a mass-spring system. The exact contour of each ROI is first obtained using a geodesic active contour model. The ROI is then parameterized by the vibration modes resulting from the deformation process. Once each structure has been defined, the method provides a 3D global model including the whole set of ROIs. This model allows one to describe statistically the most significant variations among its structures. Statistical ROI variations among a set of patients or through time can be analyzed. Experimental results are presented using the pelvic zone to simulate anatomical variations among structures and its application in radiotherapy treatment planning.

Conditional gene expression in invertebrate animal models

A mechanistic understanding of biology requires appreciating spatiotemporal aspects of gene expression and its functional implications.Conditional expression allows for (ir)reversible switching of genes on or off,with the potential of spatial and/or temporal control.This provides a valuable complement to the more often used constitutive gene (in)activation through mutagenesis,providing tools to answer a wider array of research questions across biological disciplines.Spatial and/or temporal control are granted primarily by(combinations of) specific promoters,temperature regimens,compound addition,or illumination.The use of such genetic tool kits is particularly widespread in invertebrate animal models because they can be applied to study biological processes in short time frames and on large scales,using organisms amenable to easy genetic manipulation.Recent years witnessed an exciting expansion and optimization of such tools,of which we provide a comprehensive overview and discussion regarding their use in invertebrates.The mechanism,applicability,benefits,and drawbacks of each of the systems,as well as further developments to be expected in the foreseeable future,are highlighted.