Three-dimensional models of antigens with serodiagnostic potential for leprosy:An in silico study

BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.

Three-Dimensional Models for Analyzing the Cyclic Variations in a Lean Burn CNG Engine

Three-dimensional models, consisting of the flame kernel formation model, flame kernel development model and natural gas single step reaction model, are used to analyze the contribution of cyclic equivalence ratio variations to cyclic variations in the compressed natural gas （CNG） lean burn spark ignition engine. Computational results including the contributions of equivalence ratio cyclic variations to each combustion stage and effects of engine speed to the extent of combustion variations are discussed. It is concluded that the equivalence ratio variations affect mostly the main stage of combustion and hardly influence initial kernel development stage.

Three-dimensional structural models,evolution and petroleum geological significances of transtensional faults in the Ziyang area,central Sichuan Basin,SW China

With drilling and seismic data of Transtensional(strike-slip)Fault System in the Ziyang area of the central Sichuan Basin,SW China plane-section integrated structural interpretation,3-D fault framework model building,fault throw analyzing,and balanced profile restoration,it is pointed out that the transtensional fault system in the Ziyang 3-D seismic survey consists of the northeast-trending F_(I)19 and F_(I)20 fault zones dominated by extensional deformation,as well as 3 sets of northwest-trending en echelon normal faults experienced dextral shear deformation.Among them,the F_(I)19 and F_(I)20 fault zones cut through the Neoproterozoic to Lower Triassic Jialingjiang Formation,presenting a 3-D structure of an“S”-shaped ribbon.And before Permian and during the Early Triassic,the F_(I)19 and F_(I)20 fault zones underwent at least two periods of structural superimposition.Besides,the 3 sets of northwest-trending en echelon normal faults are composed of small normal faults arranged in pairs,with opposite dip directions and partially left-stepped arrangement.And before Permian,they had formed almost,restricting the eastward growth and propagation of the F_(I)19 fault zone.The F_(I)19 and F_(I)20 fault zones communicate multiple sets of source rocks and reservoirs from deep to shallow,and the timing of fault activity matches well with oil and gas generation peaks.If there were favorable Cambrian-Triassic sedimentary facies and reservoirs developing on the local anticlinal belts of both sides of the F_(I)19 and F_(I)20 fault zones,the major reservoirs in this area are expected to achieve breakthroughs in oil and gas exploration.

Analytical Solutions for Testing of Baroclinic and Wind-Driven Three-Dimensional Hydrodynamic Models

It is always a challenge for a model developer to verify a three-dimensional hydrodynamic model, especially for the baroclinic term over variable topography, due to a lack of observational data sets or suitable analytical solutions. In this paper, exact solutions for the periodic forcing by surface heat flux and wind stress are given by solving the linearized equations of motion neglecting the rotation, advection and horizontal diffusion terms. The temperature at the bottom is set to a prescribed periodic value and a slip condition on flow is enforced at the bottom. The geometry of the quarter annulus, which has been extensively studied for two- and three-dimensional analytical solutions of unstratified water bodies, is used with a general power law variation of the bottom slope in the radial direction and is constant in the azimuthal direction. The analytical solutions are derived in a cylindrical coordinate system, which describes the three-dimensional fluid field in a Cartesian coordinate system. The results presented in this paper should provide a foundation for studying and verifying the baroclinic term over a varied topography in a three-dimensional numerical model.

The Impact of The Three-Dimensional Cultivation Model on the Development of the Suzhou Tea Industry:Estimating Value of Output Per Acre and Diversified Sales Models

This article explores the impact of the three-dimensional cultivation mode on the development of the Suzhou tea industry,focusing on the diversified estimation of the value of output per acre and sales mode.It introduces the history and traditional cultivation practices of tea in Suzhou,as well as the current challenges and problems faced by the industry.An in-depth analysis was conducted on the overview and improvement plans of the three-dimensional cultivation mode,covering relevant technical methods.Based on this analysis,the impact of the three-dimensional cultivation on the value of output per acre was studied and predicted.Its potential and advantages were explored and compared with the effectiveness of traditional cultivation models.Additionally,the impact of the three-dimensional cultivation mode on sales was analyzed,examining its market adaptability and competitiveness,as well as its advantages in expanding sales channels and market coverage.The study also focused on the promoting effect of diversified sales models on the Suzhou tea industry,including direct consumption market development,tea processing product development and promotion,and the integration of tea culture and the tourism industry.To ensure sustainable development,the article evaluates the environmental impact,economic feasibility,social benefits,and farmer benefits of the three-dimensional cultivation model.Finally,the prospects for the development of the Suzhou tea industry were discussed,and the positioning and response strategies of the threedimensional cultivation model were proposed.

Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

Three-dimensional Modeling of Ore-forming Elements and Mineralization Prognosis for the Yechangping Mo Deposit,Henan Province,China

Three-dimensional geochemical modeling of ore-forming elements is crucial for predicting deep mineralization.This approach provides key information for the quantitative prediction of deep mineral localization,three-dimensional fine interpolation,analysis of spatial distribution patterns,and extraction of quantitative mineral-seeking markers.The Yechangping molybdenum(Mo)deposit is a significant and extensive porphyry-skarn deposit in the East Qinling-Dabie Mo polymetallic metallogenic belt at the southern margin of the North China Block.Abundant borehole data on oreforming elements underpin deep geochemical predictions.The methodology includes the following steps:(1)Threedimensional geological modeling of the deposit was established.(2)Correlation,cluster,and factor analyses post delineation of mineralization stages and determination of mineral generation sequence to identify(Cu,Pb,Zn,Ag)and(Mo,W,mfe)assemblages.(3)A three-dimensional geochemical block model was constructed for Mo,W,mfe,Cu,Zn,Pb,and Ag using the ordinary kriging method,and the variational function was developed.(4)Spatial distribution and enrichment characteristics analysis of ore-forming elements are performed to extract geological information,employing the variogram and w(Cu+Pb+Zn+Ag)/w(Mo+W)as predictive indicators.(5)Identifying the western,northwestern,and southwestern areas of the mine with limited mineralization potential,contrasted by the northeastern and southeastern areas favorable for mineral exploration.

Numerical three-dimensional modeling of earthen dam piping failure

A physically-based numerical three-dimensional earthen dam piping failure model is developed for homogeneous and zoned soil dams.This model is an erosion model,coupled with force/moment equilibrium analyses.Orifice flow and two-dimensional(2D)shallow water equations(SWE)are solved to simulate dam break flows at different breaching stages.Erosion rates of different soils with different construction compaction efforts are calculated using corresponding erosion formulae.The dam's real shape,soil properties,and surrounding area are programmed.Large outer 2D-SWE grids are used to control upstream and downstream hydraulic conditions and control the boundary conditions of orifice flow,and inner 2D-SWE flow is used to scour soil and perform force/moment equilibrium analyses.This model is validated using the European Commission IMPACT(Investigation of Extreme Flood Processes and Uncertainty)Test#5 in Norway,Teton Dam failure in Idaho,USA,and Quail Creek Dike failure in Utah,USA.All calculated peak outflows are within 10%errors of observed values.Simulation results show that,for a V-shaped dam like Teton Dam,a piping breach location at the abutment tends to result in a smaller peak breach outflow than the piping breach location at the dam's center;and if Teton Dam had broken from its center for internal erosion,a peak outflow of 117851 m'/s,which is 81%larger than the peak outflow of 65120 m3/s released from its right abutment,would have been released from Teton Dam.A lower piping inlet elevation tends to cause a faster/earlier piping breach than a higher piping inlet elevation.

Can preoperative planning using IRIS™three-dimensional anatomical virtual models predict operative findings during robot-assisted partial nephrectomy?

Objective To evaluate the predictive validity of IRIS™(Intuitive Surgical®,Sunnyvale,CA,USA)as a planning tool for robot-assisted partial nephrectomy(RAPN)by assessing the degree of overlap with intraoperative execution.Methods Thirty-one patients scheduled for RAPN by four experienced urologists were enrolled in a prospective study.Prior to surgery,urologists reviewed the IRIS™three-dimensional model on an iphone Operating System(iOS)app and completed a questionnaire outlining their surgical plan including surgical approach,and ischemia technique as well as confidence in executing this plan.Postoperatively,questionnaires assessing the procedural approach,clinical utility,efficiency,and effectiveness of IRIS™were completed.The degree of overlap between the preoperative and intraoperative questionnaires and between the planned approach and actual execution of the procedure was analyzed.Questionnaires were answered on a 5-point Likert scale and scores of 4 or greater were considered positive.Results Mean age was 65.1 years with a mean tumor size of 27.7 mm(interquartile range 17.5-44.0 mm).Hilar tumors consisted of 32.3%;48.4%of patients had R.E.N.A.L.nephrometry scores of 7-9.On preoperative questionnaires,the surgeons reported that in 67.7%cases they were confident that they can perform the procedure successfully,and on intraoperative questionnaires,the surgeons reported that in 96.8%cases IRIS™helped achieve good spatial sensation of the anatomy.There was a high degree of overlap between preoperative and intraoperative questionnaires for the surgical approach,interpreting anatomical details and clinical utility.When comparing plans for selective or off-clamp,the preoperative plan was executed in 90.0%of cases intraoperatively.Conclusion A high degree of overlap between the preoperative surgical approach and intraoperative RAPN execution was found using IRIS™.This is the first study to evaluate the predictive accuracy of IRIS™during RAPN by comparing preoperative plan and intraoperative execution.

A theory for three-dimensional response of micropolar plates

Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.

Three-dimensional cell-based strategies for liver regeneration

Liver regeneration and the development of effective therapies for liver failure remain formidable challenges in modern medicine.In recent years,the utilization of 3D cell-based strategies has emerged as a promising approach for addressing these urgent clinical requirements.This review provides a thorough analysis of the application of 3D cell-based approaches to liver regeneration and their potential impact on patients with end-stage liver failure.Here,we discuss various 3D culture models that incorporate hepatocytes and stem cells to restore liver function and ameliorate the consequences of liver failure.Furthermore,we explored the challenges in transitioning these innovative strategies from preclinical studies to clinical applications.The collective insights presented herein highlight the significance of 3D cell-based strategies as a transformative paradigm for liver regeneration and improved patient care.

Anisotropic time-dependent behaviors of shale under direct shearing and associated empirical creep models

Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.

Evolution and Prospects of Foundation Models: From Large Language Models to Large Multimodal Models

Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.

Effects of three-dimensional quality assessment nursing intervention on efficacy and disease management of patients undergoing esophageal cancer surgery

BACKGROUND Esophageal cancer is one of the most common malignant tumors.The three-dimensional quality structure model is a quality assessment theory that includes three dimensions:Structure,process,and results.AIM To investigate the effects of nursing interventions with three-dimensional quality assessment on the efficacy and disease management ability of patients undergoing esophageal cancer surgery.METHODS In this prospective study,the control group received routine nursing,and the intervention group additionally received a three-dimensional quality assessment intervention based on the above routine care.Self-efficacy and patient disease management abilities were evaluated using the General Self-Efficacy Scale(GSES)and Exercise of Self-Care Agency scale,respectively.IBM SPSS Statistics for Windows,version 17.0,was used for the data processing.RESULTS This study recruited 112 patients who were assigned to the control and experi-mental groups(n=56 per group).Before the intervention,there was no significant difference in GSES scores between the two groups(P>0.05).After the inter-vention,the GSES scores of both groups increased,with the experimental group showing higher values(P<0.05).At the time of discharge and three months after discharge,the scores for positive attitudes,self-stress reduction,and total score of health promotion in the experimental group were higher than those in the control group(P<0.05).CONCLUSION The implementation of a three-dimensional quality structure model for postoperative patients with esophageal cancer can effectively improve their self-management ability and self-efficacy of postoperative patients.

The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Assessing the Performance of CMIP6 Models in Simulating Droughts across Global Drylands

Both the attribution of historical change and future projections of droughts rely heavily on climate modeling. However,reasonable drought simulations have remained a challenge, and the related performances of the current state-of-the-art Coupled Model Intercomparison Project phase 6(CMIP6) models remain unknown. Here, both the strengths and weaknesses of CMIP6 models in simulating droughts and corresponding hydrothermal conditions in drylands are assessed.While the general patterns of simulated meteorological elements in drylands resemble the observations, the annual precipitation is overestimated by ~33%(with a model spread of 2.3%–77.2%), along with an underestimation of potential evapotranspiration(PET) by ~32%(17.5%–47.2%). The water deficit condition, measured by the difference between precipitation and PET, is 50%(29.1%–71.7%) weaker than observations. The CMIP6 models show weaknesses in capturing the climate mean drought characteristics in drylands, particularly with the occurrence and duration largely underestimated in the hyperarid Afro-Asian areas. Nonetheless, the drought-associated meteorological anomalies, including reduced precipitation, warmer temperatures, higher evaporative demand, and increased water deficit conditions, are reasonably reproduced. The simulated magnitude of precipitation(water deficit) associated with dryland droughts is overestimated by 28%(24%) compared to observations. The observed increasing trends in drought fractional area,occurrence, and corresponding meteorological anomalies during 1980–2014 are reasonably reproduced. Still, the increase in drought characteristics, associated precipitation and water deficit are obviously underestimated after the late 1990s,especially for mild and moderate droughts, indicative of a weaker response of dryland drought changes to global warming in CMIP6 models. Our results suggest that it is imperative to employ bias correction approaches in drought-related studies over drylands by using CMIP6 outputs.

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.