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

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

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

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

Effect of information-motivation-behavioral skills model based perioperative nursing on pain in patients with gallstones

BACKGROUND The incidence of cholecystolithiasis is on the rise.Use of information,motivation,and behavioral skills can play a positive role in promoting changes in individual health behaviors.However,reports on the effects of information-motivationbehavioral(IMB)skills model based high-quality nursing as a perioperative nursing intervention for patients with gallstones are nonexistent.AIM To explore the application of IMB skills model based high-quality nursing in patients with gallstones.METHODS Two hundred and sixteen patients with cholecystolithiasis treated at our hospital from January 2022 to January 2023 were enrolled and divided into a control,highquality,and combined nursing groups,with 72 patients in each group.The control,high-quality,and combination groups received conventional,high-quality,and IMB skills model based perioperative nursing services,respectively.Differences in clinical indicators,stress levels,degree of pain,emotional state,and quality of life were observed,and complications and nursing satisfaction among the three groups were evaluated.RESULTS After nursing,the time to recovery of gastrointestinal function in the high-quality and combined nursing groups was significantly shorter than that of the control group,with the recovery of gastrointestinal function being the fastest in the combined nursing group(P<0.05).After nursing intervention,cortisol and norepinephrine levels in the high-quality and combined nursing groups were closer to normal than those of the control group 24 h after surgery,with the combined nursing group having the closest to normal levels(P<0.05).After 3 and 7 d of intervention,the patients’pain significantly improved,which was more prominent in the highquality and combination groups.Meanwhile,the pain score in the combination group was significantly lower than those of the control and high-quality nursing groups(P<0.05).After nursing intervention,the emotional states of all patients improved,and the scores of patients in the combination group were significantly lower than those of the control and high-quality nursing groups.The quality of life of patients in the high-quality and combined nursing groups significantly improved after nursing intervention compared to that of the control group,with the combined nursing group having the highest quality of life score.After intervention,the incidence of complications in the high-quality and combination groups was significantly lower than that of the control group(P<0.05),but the difference between the combination and high-quality nursing groups was not significant.Nursing satisfaction of patients in the high-quality and combination groups was significantly higher than that of the control group,with the nursing satisfaction being the highest in the combination group(P<0.05).CONCLUSION IMB skills model based nursing can improve surgical stress levels,degrees of pain,emotional state,quality of life,and nursing satisfaction of patients with gallstones and reduce the incidence of complications.

Parameter calibration of the tensile-shear interactive damage constitutive model for sandstone failure

The tensile-shear interactive damage(TSID)model is a novel and powerful constitutive model for rock-like materials.This study proposes a methodology to calibrate the TSID model parameters to simulate sandstone.The basic parameters of sandstone are determined through a series of static and dynamic tests,including uniaxial compression,Brazilian disc,triaxial compression under varying confining pressures,hydrostatic compression,and dynamic compression and tensile tests with a split Hopkinson pressure bar.Based on the sandstone test results from this study and previous research,a step-by-step procedure for parameter calibration is outlined,which accounts for the categories of the strength surface,equation of state(EOS),strain rate effect,and damage.The calibrated parameters are verified through numerical tests that correspond to the experimental loading conditions.Consistency between numerical results and experimental data indicates the precision and reliability of the calibrated parameters.The methodology presented in this study is scientifically sound,straightforward,and essential for improving the TSID model.Furthermore,it has the potential to contribute to other rock constitutive models,particularly new user-defined models.

Investigation of FRP and SFRC Technologies for Efficient Tunnel Reinforcement Using the Cohesive Zone Model

Amid urbanization and the continuous expansion of transportation networks,the necessity for tunnel construction and maintenance has become paramount.Addressing this need requires the investigation of efficient,economical,and robust tunnel reinforcement techniques.This paper explores fiber reinforced polymer(FRP)and steel fiber reinforced concrete(SFRC)technologies,which have emerged as viable solutions for enhancing tunnel structures.FRP is celebrated for its lightweight and high-strength attributes,effectively augmenting load-bearing capacity and seismic resistance,while SFRC’s notable crack resistance and longevity potentially enhance the performance of tunnel segments.Nonetheless,current research predominantly focuses on experimental analysis,lacking comprehensive theoretical models.To bridge this gap,the cohesive zone model(CZM),which utilizes cohesive elements to characterize the potential fracture surfaces of concrete/SFRC,the rebar-concrete interface,and the FRP-concrete interface,was employed.A modeling approach was subsequently proposed to construct a tunnel segment model reinforced with either SFRC or FRP.Moreover,the corresponding mixed-mode constitutive models,considering interfacial friction,were integrated into the proposed model.Experimental validation and numerical simulations corroborated the accuracy of the proposed model.Additionally,this study examined the reinforcement design of tunnel segments.Through a numerical evaluation,the effectiveness of innovative reinforcement schemes,such as substituting concrete with SFRC and externally bonding FRP sheets,was assessed utilizing a case study from the Fuzhou Metro Shield Tunnel Construction Project.

Anxiety Mouse Model Constructed by Single Intraperitoneal Injection of m-Chlorophenpiperazine

Anxiety disorder is a common mental disorder. It is necessary to establish a rapid, stable and specific anxiety model to provide a theoretical basis for further research on the pathogenesis of anxiety and drug development. A single intraperitoneal injection of m-chlorophenylpipera-zine (mCPP) (1, 2, 4 mg/kg) was given to male ICR mice to establish an anxiety model, and the effects of mCPP on anxiety behavior, pain, athletic ability, passive avoidance response ability and depressive behavior of male ICR mice were evaluated. A single intraperitoneal injection of mCPP shortened the time in open arms and decreased the percentage of time in open arms of mice in the elevated plus-maze test. mCPP also shortened center zone distance and reduced the number of entries to the central zone in the open field test. Moreover, mCPP reduced head-dip counts and increased the head-dip latency of mice in the hole-board test. After being administrated with a single intraperitoneal injection of mCPP for 24h, the mice showed no significant difference in the entry into the light side and the percentage of time in the light side of the light-dark box test. A single intraperitoneal injection of mCPP had no effects on tail flick latency, rotating time, number of errors and the step-down latency, the immobility time of mice in the tail-flick test, rotarod test, step-down test and TST respectively. In conclusion, we established a rapid and stable anxiety mouse model by single intraperitoneal injection of mCPP.

Calculation and prediction of divertor detachment via impurity seeding by using one-dimensional model

Achieving the detachment of divertor can help to alleviate excessive heat load and sputtering problems on the target plates,thereby extending the lifetime of divertor components for fusion devices.In order to provide a fast but relatively reliable prediction of plasma parameters along the flux tube for future device design,a one-dimensional(1D)modeling code for the operating point of impurity seeded detached divertor is developed based on Python language,which is a fluid model based on previous work(Plasma Phys.Control.Fusion 58045013(2016)).The experimental observation of the onset of divertor detachment by neon(Ne)and argon(Ar)seeding in EAST is well reproduced by using the 1D modeling code.The comparison between the 1D modeling and two-dimensional(2D)simulation by the SOLPS-ITER code for CFETR detachment operation with Ne and Ar seeding also shows that they are in good agreement.We also predict the radiative power loss and corresponding impurity concentration requirement for achieving divertor detachment via different impurity seeding under high heating power conditions in EAST and CFETR phase II by using the 1D model.Based on the predictions,the optimized parameter space for divertor detachment operation on EAST and CFETR is also determined.Such a simple but reliable 1D model can provide a reasonable parameter input for a detailed and accurate analysis by 2D or three-dimensional(3D)modeling tools through rapid parameter scanning.

Thermal-contact capacity of one-dimensional attractive Gaudin-Yang model

Tan's contact C is an important quantity measuring the two-body correlations at short distances in a dilute system.Here we make use of the technique of exactly solved models to study the thermal-contact capacity K_(T),i.e.,the derivative of C with respect to temperature in the attractive Gaudin-Yang model.It is found that K_(T) is useful in identifying the low temperature phase diagram,and using the obtained analytical expression of K_(T),we study its critical behavior and the scaling law.Especially,we show K_(T) versus temperature and thus the non-monotonic tendency of C in a tiny interval,for both spin-balanced and imbalanced phases.Such a phenomenon is merely observed in multi-component systems such as SU(2)Fermi gases and spinor bosons,indicating the crossover from the Tomonaga-Luttinger liquid to the spin-coherent liquid.

Cameroon Climate Predictions Using the SARIMA-LSTM Machine Learning Model: Adjustment of a Climate Model for the Sudano-Sahelian Zone of Cameroon

It is acknowledged today within the scientific community that two types of actions must be considered to limit global warming: mitigation actions by reducing GHG emissions, to contain the rate of global warming, and adaptation actions to adapt societies to Climate Change, to limit losses and damages [1] [2]. As far as adaptation actions are concerned, numerical simulation, due to its results, its costs which require less investment than tests carried out on complex mechanical structures, and its implementation facilities, appears to be a major step in the design and prediction of complex mechanical systems. However, despite the quality of the results obtained, biases and inaccuracies related to the structure of the models do exist. Therefore, there is a need to validate the results of this SARIMA-LSTM-digital learning model adjusted by a matching approach, “calculating-test”, in order to assess the quality of the results and the performance of the model. The methodology consists of exploiting two climatic databases (temperature and precipitation), one of which is in-situ and the other spatial, all derived from grid points. Data from the dot grids are processed and stored in specific formats and, through machine learning approaches, complex mathematical equations are worked out and interconnections within the climate system established. Through this mathematical approach, it is possible to predict the future climate of the Sudano-Sahelian zone of Cameroon and to propose adaptation strategies.

Assessment of the three representative empirical models for zenith tropospheric delay(ZTD)using the CMONOC data

The precise correction of atmospheric zenith tropospheric delay(ZTD)is significant for the Global Navigation Satellite System(GNSS)performance regarding positioning accuracy and convergence time.In the past decades,many empirical ZTD models based on whether the gridded or scattered ZTD products have been proposed and widely used in the GNSS positioning applications.But there is no comprehensive evaluation of these models for the whole China region,which features complicated topography and climate.In this study,we completely assess the typical empirical models,the IGGtropSH model(gridded,non-meteorology),the SHAtropE model(scattered,non-meteorology),and the GPT3 model(gridded,meteorology)using the Crustal Movement Observation Network of China(CMONOC)network.In general,the results show that the three models share consistent performance with RMSE/bias of 37.45/1.63,37.13/2.20,and 38.27/1.34 mm for the GPT3,SHAtropE and IGGtropSH model,respectively.However,the models had a distinct performance regarding geographical distribution,elevation,seasonal variations,and daily variation.In the southeastern region of China,RMSE values are around 50 mm,which are much higher than that in the western region,approximately 20 mm.The SHAtropE model exhibits better performance for areas with large variations in elevation.The GPT3 model and the IGGtropSH model are more stable across different months,and the SHAtropE model based on the GNSS data exhibits superior performance across various UTC epochs.

Mechanical behavior and damage constitutive model of sandstone under hydro-mechanical (H-M) coupling

Underground engineering often passes through water-rich fractured rock masses, which are prone to fracture and instability under the long-term coupling of in-situ stress field and pore water(P-W) pressure, ultimately threatening the stability of underground structures. In order to explore the mechanical properties of rocks under H-M coupling, the corresponding damage constitutive(D-C) model has become the focus of attention. Considering the inadequacy of the current research on rock strength parameters,energy evolution characteristics and D-C model under H-M coupling, the mechanical properties of typical sandstone samples are discussed based on laboratory tests. The results show that the variation of characteristic stresses of sandstone under H-M coupling conforms to the normalized attenuation equation and Mohr-Coulomb(M-C) criterion. The P-W pressure mechanism of sandstone exhibits a dynamic change from softening effect to H-M fracturing effect. The closure stress is mainly provided by cohesive strength, while the initiation stress, damage stress, and peak stress are jointly dominated by cohesive strength and friction strength. In addition, residual stress is attributed to the friction strength formed by the bite of the fracture surface. Subsequently, the energy evolution characteristics of sandstone under H-M coupling were studied, and it was found that P-W pressure weakened the energy storage capacity and energy dissipation capacity of sandstone, and H-M fracturing was an important factor in reducing its energy storage efficiency. Finally, combined with energy dissipation theory and statistical damage theory, two types of D-C models considering P-W pressure are proposed accordingly, and the model parameters can be determined by four methods. The application results indicate that the proposed and modified D-C models have high reliability, and can characterize the mechanical behavior of sandstone under H-M coupling, overcome the inconvenience of existing D-C models due to excessive mechanical parameters,and can be applied to the full-range stress–strain process. The results are conducive to revealing the deformation and damage mechanisms of rocks under H-M coupling, and can provide theoretical guidance for related engineering problems.

Multi-scenario Simulation and Spatial-temporal Analysis of LUCC in China's Coastal Zone Based on Coupled SD-FLUS Model

Increased human activities in China's coastal zone have resulted in the depletion of ecological land resources.Thus,conducting current and future multi-scenario simulation research on land use and land cover change(LUCC)is crucial for guiding the healthy and sustainable development of coastal zones.System dynamic(SD)-future land use simulation(FLUS)model,a coupled simulation model,was developed to analyze land use dynamics in China's coastal zone.This model encompasses five scenarios,namely,SSP1-RCP2.6(A),SSP2-RCP4.5(B),SSP3-RCP4.5(C),SSP4-RCP4.5(D),and SSP5-RCP8.5(E).The SD model simulates land use demand on an annual basis up to the year 2100.Subsequently,the FLUS model determines the spatial distribution of land use for the near term(2035),medium term(2050),and long term(2100).Results reveal a slowing trend in land use changes in China's coastal zone from 2000–2020.Among these changes,the expansion rate of construction land was the highest and exhibited an annual decrease.By 2100,land use predictions exhibit high accuracy,and notable differences are observed in trends across scenarios.In summary,the expansion of production,living,and ecological spaces toward the sea remains prominent.Scenario A emphasizes reduced land resource dependence,benefiting ecological land protection.Scenario B witnesses an intensified expansion of artificial wetlands.Scenario C sees substantial land needs for living and production,while Scenario D shows coastal forest and grassland shrinkage.Lastly,in Scenario E,the conflict between humans and land intensifies.This study presents pertinent recommendations for the future development,utilization,and management of coastal areas in China.The research contributes valuable scientific support for informed,long-term strategic decision making within coastal regions.

An agent-based model of agricultural land expansion in the mountain forest of Timor Island,Indonesia

The Mutis-Timau Forest Complex,located on Timor Island,Indonesia,is a mountainous tropical forest area that gradually decreases due to deforestation and forest degradation.Previous modelling studies based on patterns indicate that deforestation primarily occurs at lower elevations and near the boundaries of forests and settlements,often associated with shifting cultivation by local farmers.This study adopts a process-based modelling approach,specifically the agent-based model,to simulate land changes,particularly farmers'expansion of agricultural land around the Mutis mountain forest.The underlying concept of this agent-based approach is the interaction between the human and environmental systems.Farmers,representing the human system,interact with the land,which represents the environmental system,through land use decision-making mechanisms.The research was conducted in the Community Forest of the Timor Tengah Utara District,one of the sites within the Mutis-Timau Forest Complex with the highest deforestation rate.Land use change simulations were performed using agent-based modelling from 1999 to 2030,considering the socio-economic conditions of farmers,spatial preferences,land use decisions,and natural transitions.The results revealed that the agricultural area increased by 14%under the Business as Usual scenario and 5%under the Reducing Emission from Deforestation and Forest Degradation scenario,compared to the initial agricultural area of 245 hectares.The probability of farmers deciding to extend agricultural activities was positively associated with the number of livestock maintained by farmers and the size of the village area.Conversely,the likelihood of farmers opting for agricultural extensification decreased with an increase in the area of private land and the farmer's age.These findings are crucial for the managers of the Mutis-Timau Forest Complex and other relevant stakeholders,as they aid in arranging actions to combat deforestation,designing proper forest-related policies,and providing support for initiatives such as reducing emissions from deforestation and forest degradation programs or further incentive schemes.

Investigation of Maxima Assumptions in Modelling Tropical Cyclone- Induced Hazards in the South China Sea

The present study aims to examine the suitability of two commonly used assumptions that simplify modelling metoceanconditions for designing offshore wind turbines in the South China Sea (SCS). The first assumption assumes thatjoint N-year extreme wind and wave events can be independently estimated and subsequently combined. The secondone assumes peak wind and waves can be modelled as occurring simultaneously during a tropical cyclone (TC) event.To better understand the potential TC activity, a set of 10000 years synthetic TC events are generated. The wind fieldmodel and the Mike 21 spectral wave model are employed to model the TC-induced hazards. Subsequently, theeffect of the assumptions is evaluated by analyzing the peak structural response of both monopile and semisubmersibleoffshore wind turbines during TC events. The results demonstrate that the examined assumptions are generally accurate.By assessing the implications of these assumptions, valuable insights are obtained, which can inform andimprove the modelling of TC-induced hazards in the SCS region.

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.

Evaluation of Serum Anti-Müllerian Hormone (AMH) Values for 28,016 Bulgarian Women: Prognostic Statistical Model of Age Specific AMH Declining

The present study aims to establish a relationship between serum AMH levels and age in a large group of women living in Bulgaria, as well as to establish reference age-specific AMH levels in women that would serve as an initial estimate of ovarian age. A total of 28,016 women on the territory of the Republic of Bulgaria were tested for serum AMH levels with a median age of 37.0 years (interquartile range 32.0 to 41.0). For women aged 20 - 29 years, the Bulgarian population has relatively high median levels of AMH, similar to women of Asian origin. For women aged 30 - 34 years, our results are comparable to those of women living in Western Europe. For women aged 35 - 39 years, our results are comparable to those of women living in the territory of India and Kenya. For women aged 40 - 44 years, our results were lower than those for women from the Western European and Chinese populations, close to the Indian and higher than Korean and Kenya populations, respectively. Our results for women of Bulgarian origin are also comparable to US Latina women at age 30, 35 and 40 ages. On the base on constructed a statistical model to predicting the decline in AMH levels at different ages, we found non-linear structure of AMH decline for the low AMH 3.5) the dependence of the decline of AMH on age was confirmed as linear. In conclusion, we evaluated the serum level of AMH in Bulgarian women and established age-specific AMH percentile reference values based on a large representative sample. We have developed a prognostic statistical model that can facilitate the application of AMH in clinical practice and the prediction of reproductive capacity and population health.

Locally and globally uniform approximations for ruin probabilities of a nonstandard bidimensional risk model with subexponential claims

Consider a nonstandard continuous-time bidimensional risk model with constant force of interest,in which the two classes of claims with subexponential distributions satisfy a general dependence structure and each pair of the claim-inter-arrival times is arbitrarily dependent.Under some mild conditions,we achieve a locally uniform approximation of the finite-time ruin probability for all time horizon within a finite interval.If we further assume that each pair of the claim-inter-arrival times is negative quadrant dependent and the two classes of claims are consistently-varying-tailed,it shows that the above obtained approximation is also globally uniform for all time horizon within an infinite interval.

Modelling the viscoplastic behaviour of Callovo-Oxfordian claystone with consideration of damage effect

In order to evaluate the performance of deep geological disposal of radioactive waste,an underground research laboratory(URL)was constructed by Andra in the Callovo-Oxfordian(COx)claystone formation at the Meuse/Haute-Marne(MHM).The construction of URL induced the excavation damage of host formations,and the ventilation in the galleries desaturated the host formation close to the gallery wall.Moreover,it is expected that the mechanical behaviour of COx claystone is time-dependent.This study presents a constitutive model developed to describe the viscoplastic behaviour of unsaturated and damaged COx claystone.In this model,the unsaturation effect is considered by adopting the Bishop effective stress and the van Genuchten(VG)water retention model.In terms of the viscoplastic behaviour,the nonstationary flow surface(NSFS)theory for unsaturated soils is used with consideration of the coupled effects of strain rate and suction on the yield stress.A progressive hardening law is adopted.Meanwhile,a non-associated flow rule is used,which is similar to that in Barcelona basic model(BBM).In addition,to describe the damage effect induced by suction change and viscoplastic loading,a damage function is defined based on the crack volume proportion.This damage function contains two variables:unsaturated effective stress and viscoplastic volumetric strain,with the related parameters determined based on the mercury intrusion porosimetry(MIP)tests.For the model validation,different tests on COx claystone under different loading paths are simulated.Comparisons between experimental and simulated results indicated that the present model is able to well describe the viscoplastic behaviour of damaged COx claystone,including swelling/shrinkage,triaxial extension and compression,and triaxial creep.

The bio-active components of the Mongolian medicine Horcha-6 and therapeutic mechanism in the rat migraine model

Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.

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.