The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic fu...The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.展开更多
Cylindrical vector beams(CVBs)hold significant promise in mode division multiplexing communication owing to their inherent vector mode orthogonality.However,existing studies for facilitating CVB channel processing are...Cylindrical vector beams(CVBs)hold significant promise in mode division multiplexing communication owing to their inherent vector mode orthogonality.However,existing studies for facilitating CVB channel processing are confined to mode shift conversions due to their reliance on spin-dependent helical modulations,overlooking the pursuit of mode multiplication conversion.This challenge lies in the multiplicative operation upon inhomogeneous vector mode manipulation,which is expected to advance versatile CVB channel switching and routing.Here,we tackle this gap by introducing a raytracing control strategy that conformally maps the light rays of CVB from the whole annulus distribution to an annular sector counterpart.Incorporated with the multifold conformal annulus-sector mappings and polarization-insensitive phase modulations,this approach facilitates the parallel transformation of input CVB into multiple complementary components,enabling the mode multiplication conversion with protected vector structure.Serving as a demonstration,we experimentally implemented the multiplicative operation of four CVB modes with the multiplier factors of N=+2 and N=−3,achieving the converted mode purities over 94.24%and 88.37%.Subsequently,200 Gbit/s quadrature phase shift keying signals were successfully transmitted upon multiplicative switching of four CVB channels,with the bit-error-rate approaching 1×10^(−6).These results underscore our strategy’s efficacy in CVB mode multiplication,which may open promising prospects for its advanced applications.展开更多
This paper provides a method of the process of computation called the cumulative method, it is based upon repeated cumulative process. The cumulative method is being adapted to the purposes of computation, particularl...This paper provides a method of the process of computation called the cumulative method, it is based upon repeated cumulative process. The cumulative method is being adapted to the purposes of computation, particularly multiplication and division. The operations of multiplication and division are represented by algebraic formulas. An advantage of the method is that the cumulative process can be performed on decimal numbers. The present paper aims to establish a basic and useful formula valid for the two fundamental arithmetic operations of multiplication and division. The new cumulative method proved to be more flexible and made it possible to extend the multiplication and division based on repeated addition/subtraction to decimal numbers.展开更多
In this paper,we study multiplication operators on weighted Dirichlet spaces D_(β)(β∈R).Let n be a positive integer and β∈R,we show that the multiplication operator M_(z)^(n) on D_(β) is similar to the operator ...In this paper,we study multiplication operators on weighted Dirichlet spaces D_(β)(β∈R).Let n be a positive integer and β∈R,we show that the multiplication operator M_(z)^(n) on D_(β) is similar to the operator ⊕_(1)^(n)M_(z)on the space⊕_(1)^(n)D_(β).Moreover,we prove that M_(z)^(n)(≥2)on Dβis unitarily equivalent to ⊕_(1)^(n)M_(z) on⊕_(1)^(n)D_(β) if and only if β=0.In addition,we completely characterize the unitary equivalence of the restrictions of M_(z)^(n) to different invariant subspaces z^(k)D_(β)(k≥1),and the unitary equivalence of the restrictions of M_(z)^(n) to different invariant subspaces S_(j)(0≤j<n).Abkar,Cao and Zhu[Complex Anal Oper Theory,2020,14:Art 58]pointed out that it is an important,natural,and difficult question in operator theory to identify the commutant of a bounded linear operator.They characterized the commutant A′( M_(z)^(n))of M_(z)^(n)on a family of analytic function spaces A_(α)^(2)(α∈R)on D(in fact,the family of spaces A_(α)^(2)(α∈R)is the same with the family of spaces D_(β)(β∈R))in terms of the multiplier algebra of the underlying function spaces.In this paper,we give a new characterization of the commutant A′( M_(z)^(n))of M_(z)^(n)on D_(β),and characterize the self-adjoint operators and unitary operators in A'(M_(z)^(n)).We find that the class of self-adjoint operators(unitary operators)in A'(M_(z)^(n))when β≠0 is different from the class of self-adjoint operators(unitary operators)in A′( M_(z)^(n))when β=0.展开更多
Video watermarking plays a crucial role in protecting intellectual property rights and ensuring content authenticity.This study delves into the integration of Galois Field(GF)multiplication tables,especially GF(2^(4))...Video watermarking plays a crucial role in protecting intellectual property rights and ensuring content authenticity.This study delves into the integration of Galois Field(GF)multiplication tables,especially GF(2^(4)),and their interaction with distinct irreducible polynomials.The primary aim is to enhance watermarking techniques for achieving imperceptibility,robustness,and efficient execution time.The research employs scene selection and adaptive thresholding techniques to streamline the watermarking process.Scene selection is used strategically to embed watermarks in the most vital frames of the video,while adaptive thresholding methods ensure that the watermarking process adheres to imperceptibility criteria,maintaining the video's visual quality.Concurrently,careful consideration is given to execution time,crucial in real-world scenarios,to balance efficiency and efficacy.The Peak Signal-to-Noise Ratio(PSNR)serves as a pivotal metric to gauge the watermark's imperceptibility and video quality.The study explores various irreducible polynomials,navigating the trade-offs between computational efficiency and watermark imperceptibility.In parallel,the study pays careful attention to the execution time,a paramount consideration in real-world scenarios,to strike a balance between efficiency and efficacy.This comprehensive analysis provides valuable insights into the interplay of GF multiplication tables,diverse irreducible polynomials,scene selection,adaptive thresholding,imperceptibility,and execution time.The evaluation of the proposed algorithm's robustness was conducted using PSNR and NC metrics,and it was subjected to assessment under the impact of five distinct attack scenarios.These findings contribute to the development of watermarking strategies that balance imperceptibility,robustness,and processing efficiency,enhancing the field's practicality and effectiveness.展开更多
This paper aims to treat a study of generators of the cyclic group of higher even, odd, and prime order for composition being multiplication. In fact we developed order of a group, order of element of a group and gene...This paper aims to treat a study of generators of the cyclic group of higher even, odd, and prime order for composition being multiplication. In fact we developed order of a group, order of element of a group and generators of the cyclic group in real numbers. Also we express cyclic and generators of the group for composition in real numbers. Here we discuss the higher order of groups in different types of order, and generators of the cyclic group which will give us practical knowledge to see the applications of the composition. In order to find out the order of an element am∈Gin which an=e= identity element, then find Highest Common Factor i.e. (H.C.F) of mand n. When Gis a finite group, every element must have finite order but the converse is false. There are infinite groups where each element has a finite order. There may be more than one generator of a cyclic group. Also every cyclic group is necessarily abelian. But show that every infinite cyclic group contains only two generators. Finally, we find out the generators of the cyclic group of higher even, odd and prime order in different types of the group for composition being multiplication.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to d...This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.展开更多
In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology bas...In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the ex...Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM(NDMM)patients,and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM.Methods:A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled.Five key immunophenotypic markers(including CD38,CD138,CD45,CD56,and CD200)were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis.Patients were divided into 3 groups:Group A,CD45 and CD200 double-positive;Group B,CD45 or CD200 single-positive;Group C,CD45 and CD200 double-negative.Kaplan-Meier curves were used to analyze overall survival(OS)and progression-free survival(PFS)across groups.Multivariate Cox regression was performed to evaluate prognostic factors,and a nomogram was constructed based on these results.Results:The OS and PFS of single-positive groups for CD38,CD138,CD45,CD56,and CD200 were all shorter than those of their respective single-negative groups(all P<0.05).Significant differences were observed in OS(P<0.001)and PFS(P=0.001)among Groups A,B,and C.Group A had shorter OS and PFS(all P=0.001)compared to the Group B+C(cases from Group B and Group C were combined).CD45 and CD200 double-positive was an independent prognostic factor for NDMM[hazard ratio(HR)=2.178,95%confidence interval(CI)1.048 to 4.529;P=0.037].The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance(concordance index=0.706;95%CI 0.661 to 0.751).Conclusion:NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS.Compared with the use of either marker alone,the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.展开更多
The charge carrier transport and recombination dynamics in the quantum dots-based light-emitting diodes(QLEDs)featuring multiple emitting layers(M-EMLs)has a great impact on the device performance.In this work,QLEDs b...The charge carrier transport and recombination dynamics in the quantum dots-based light-emitting diodes(QLEDs)featuring multiple emitting layers(M-EMLs)has a great impact on the device performance.In this work,QLEDs based on M-EMLs separated by polyethyleneimine ethoxylated(PEIE)layer with different stacking sequences of blue(B),green(G),and red(R)QDs layer were used to intuitively explore the injection,transportation and recombination processes of the charge carriers in QLEDs by using the time-resolved electroluminescence(TrEL)spectra.From the TrEL spectra mea-surements,green and red emissions were obtained first in the QLEDs with the EMLs sequences of G/PEIE/B/PEIE/R and B/PEIE/R/PEIE/G along the direction of light emission,respectively.While the QLEDs adopt EMLs sequences of B/PEIE/G/PEIE/R,the blue,green and red emissions were obtained nearly at the same time.The above phenomenon can be attributed to different charge carrier transmission and radiation recombination process in the EMLs due to different valence band offsets and conduction band offsets between R-,G-and B-QDs by using different sequences of EMLs.White emission with coordi-nates of(0.31,0.31)and correlated color temperature(CCT)of 5916 K was obtained in the QLEDs with the EMLs se-quences of B/PEIE/G/PEIE/R,which can be attributed to the relative uniform emission of B-,G-and R-QDs due to the effec-tive injection and radiation recombination of charge carriers in each of the EMLs.The above results have great significance for further understanding and improving the performance of QLEDs with M-EMLs.展开更多
Dear Editor,This letter addresses the impulse game problem for a general scope of deterministic,multi-player,nonzero-sum differential games wherein all participants adopt impulse controls.Our objective is to formulate...Dear Editor,This letter addresses the impulse game problem for a general scope of deterministic,multi-player,nonzero-sum differential games wherein all participants adopt impulse controls.Our objective is to formulate this impulse game problem with the modified objective function including interaction costs among the players in a discontinuous fashion,and subsequently,to derive a verification theorem for identifying the feedback Nash equilibrium strategy.展开更多
This paper introduces an optimized planning approach for integrating photovoltaic as distributed generation (PV-DG) into the radial distribution power systems, utilizing exhaustive load flow (ELF), loss sensitivity fa...This paper introduces an optimized planning approach for integrating photovoltaic as distributed generation (PV-DG) into the radial distribution power systems, utilizing exhaustive load flow (ELF), loss sensitivity factor (LSF), genetic algorithms (GA) methods, and numerical method based on LSF. The methodology aims to determine the optimal allocation and sizing of multiple PV-DG to minimize power loss through time series power flow analysis. An approach utilizing continuous sensitivity analysis is developed and inherently leverages power flow and loss equations to compute LSF of all buses in the system towards employing a dynamic PV-DG model for more accurate results. The algorithm uses a numerical grid search method to optimize PV-DG placement in a power distribution system, focusing on minimizing system losses. It combines iterative analysis, sensitivity assessment, and comprehensive visualization to identify and present the optimal PV-DG configurations. The present-ed algorithms are verified through co-simulation framework combining MATLAB and OpenDSS to carry out analysis for 12-bus radial distribution test system. The proposed numerical method is compared with other algorithms, such as ELF, LSF methods, and Genetic Algorithms (GA). Results show that the proposed numerical method performs well in comparison with LSF and ELF solutions.展开更多
Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesi...Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesis remains unclear,the progress in multimodal imaging(MMI)has enhanced our understanding of MEWDS.Most cases of MEWDS are idiopathic,lacking a definite cause,and can spontaneously recover;these are what we term classic MEWDS.Consequently,MEWDS is often referred to as the“common cold of the retina”.Simultaneously,patients with other disorders may present with varying degrees of manifestations similar to MEWDS.The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment.These MEWDS-like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms.Thus,they differ from classic MEWDS in certain aspects.Using the keywords“MEWDSlike”and“Secondary MEWDS”,we searched for all relevant studies published in the PubMed database from January 2021 to January 2024.Subsequently,we retrospectively summarized the clinical and imaging characteristics of MEWDS,along with the manifestations in other diseases that resembled those of MEWDS,and compared classic MEWDS with these similar presentations.Based on our review,we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis.We recommend paying close attention to patients suspected of having MEWDS,as there may be more serious systemic or ocular disorders that require prompt treatment.展开更多
Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have m...Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pa...Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.展开更多
基金Supported by Natural Science Foundation of Guangdong Province in China(2018KTSCX161)。
文摘The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.
基金supported by the National Natural Science Foundation of China(Grant No.62271322)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515030152)+1 种基金the Shenzhen Science and Technology Program(Grant No.JCYJ20210324095610027)the Natural Science Foundation of Top Talent of SZTU(Grant No.GDRC202204)。
文摘Cylindrical vector beams(CVBs)hold significant promise in mode division multiplexing communication owing to their inherent vector mode orthogonality.However,existing studies for facilitating CVB channel processing are confined to mode shift conversions due to their reliance on spin-dependent helical modulations,overlooking the pursuit of mode multiplication conversion.This challenge lies in the multiplicative operation upon inhomogeneous vector mode manipulation,which is expected to advance versatile CVB channel switching and routing.Here,we tackle this gap by introducing a raytracing control strategy that conformally maps the light rays of CVB from the whole annulus distribution to an annular sector counterpart.Incorporated with the multifold conformal annulus-sector mappings and polarization-insensitive phase modulations,this approach facilitates the parallel transformation of input CVB into multiple complementary components,enabling the mode multiplication conversion with protected vector structure.Serving as a demonstration,we experimentally implemented the multiplicative operation of four CVB modes with the multiplier factors of N=+2 and N=−3,achieving the converted mode purities over 94.24%and 88.37%.Subsequently,200 Gbit/s quadrature phase shift keying signals were successfully transmitted upon multiplicative switching of four CVB channels,with the bit-error-rate approaching 1×10^(−6).These results underscore our strategy’s efficacy in CVB mode multiplication,which may open promising prospects for its advanced applications.
文摘This paper provides a method of the process of computation called the cumulative method, it is based upon repeated cumulative process. The cumulative method is being adapted to the purposes of computation, particularly multiplication and division. The operations of multiplication and division are represented by algebraic formulas. An advantage of the method is that the cumulative process can be performed on decimal numbers. The present paper aims to establish a basic and useful formula valid for the two fundamental arithmetic operations of multiplication and division. The new cumulative method proved to be more flexible and made it possible to extend the multiplication and division based on repeated addition/subtraction to decimal numbers.
基金supported by the National Natural Science Foundation of China(12101179,12171138,12171373)the Natural Science Foundation of Hebei Province of China(A2022207001)。
文摘In this paper,we study multiplication operators on weighted Dirichlet spaces D_(β)(β∈R).Let n be a positive integer and β∈R,we show that the multiplication operator M_(z)^(n) on D_(β) is similar to the operator ⊕_(1)^(n)M_(z)on the space⊕_(1)^(n)D_(β).Moreover,we prove that M_(z)^(n)(≥2)on Dβis unitarily equivalent to ⊕_(1)^(n)M_(z) on⊕_(1)^(n)D_(β) if and only if β=0.In addition,we completely characterize the unitary equivalence of the restrictions of M_(z)^(n) to different invariant subspaces z^(k)D_(β)(k≥1),and the unitary equivalence of the restrictions of M_(z)^(n) to different invariant subspaces S_(j)(0≤j<n).Abkar,Cao and Zhu[Complex Anal Oper Theory,2020,14:Art 58]pointed out that it is an important,natural,and difficult question in operator theory to identify the commutant of a bounded linear operator.They characterized the commutant A′( M_(z)^(n))of M_(z)^(n)on a family of analytic function spaces A_(α)^(2)(α∈R)on D(in fact,the family of spaces A_(α)^(2)(α∈R)is the same with the family of spaces D_(β)(β∈R))in terms of the multiplier algebra of the underlying function spaces.In this paper,we give a new characterization of the commutant A′( M_(z)^(n))of M_(z)^(n)on D_(β),and characterize the self-adjoint operators and unitary operators in A'(M_(z)^(n)).We find that the class of self-adjoint operators(unitary operators)in A'(M_(z)^(n))when β≠0 is different from the class of self-adjoint operators(unitary operators)in A′( M_(z)^(n))when β=0.
文摘Video watermarking plays a crucial role in protecting intellectual property rights and ensuring content authenticity.This study delves into the integration of Galois Field(GF)multiplication tables,especially GF(2^(4)),and their interaction with distinct irreducible polynomials.The primary aim is to enhance watermarking techniques for achieving imperceptibility,robustness,and efficient execution time.The research employs scene selection and adaptive thresholding techniques to streamline the watermarking process.Scene selection is used strategically to embed watermarks in the most vital frames of the video,while adaptive thresholding methods ensure that the watermarking process adheres to imperceptibility criteria,maintaining the video's visual quality.Concurrently,careful consideration is given to execution time,crucial in real-world scenarios,to balance efficiency and efficacy.The Peak Signal-to-Noise Ratio(PSNR)serves as a pivotal metric to gauge the watermark's imperceptibility and video quality.The study explores various irreducible polynomials,navigating the trade-offs between computational efficiency and watermark imperceptibility.In parallel,the study pays careful attention to the execution time,a paramount consideration in real-world scenarios,to strike a balance between efficiency and efficacy.This comprehensive analysis provides valuable insights into the interplay of GF multiplication tables,diverse irreducible polynomials,scene selection,adaptive thresholding,imperceptibility,and execution time.The evaluation of the proposed algorithm's robustness was conducted using PSNR and NC metrics,and it was subjected to assessment under the impact of five distinct attack scenarios.These findings contribute to the development of watermarking strategies that balance imperceptibility,robustness,and processing efficiency,enhancing the field's practicality and effectiveness.
文摘This paper aims to treat a study of generators of the cyclic group of higher even, odd, and prime order for composition being multiplication. In fact we developed order of a group, order of element of a group and generators of the cyclic group in real numbers. Also we express cyclic and generators of the group for composition in real numbers. Here we discuss the higher order of groups in different types of order, and generators of the cyclic group which will give us practical knowledge to see the applications of the composition. In order to find out the order of an element am∈Gin which an=e= identity element, then find Highest Common Factor i.e. (H.C.F) of mand n. When Gis a finite group, every element must have finite order but the converse is false. There are infinite groups where each element has a finite order. There may be more than one generator of a cyclic group. Also every cyclic group is necessarily abelian. But show that every infinite cyclic group contains only two generators. Finally, we find out the generators of the cyclic group of higher even, odd and prime order in different types of the group for composition being multiplication.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金supported by DST-FIST(Government of India)(Grant No.SR/FIST/MS-1/2017/13)and Seed Money Project(Grant No.DoRDC/733).
文摘This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.
基金financially supported by National Key R&D Program(2021YFF0701905)。
文摘In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
基金supported by the National Natural Science Foundation,China(81870166).
文摘Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM(NDMM)patients,and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM.Methods:A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled.Five key immunophenotypic markers(including CD38,CD138,CD45,CD56,and CD200)were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis.Patients were divided into 3 groups:Group A,CD45 and CD200 double-positive;Group B,CD45 or CD200 single-positive;Group C,CD45 and CD200 double-negative.Kaplan-Meier curves were used to analyze overall survival(OS)and progression-free survival(PFS)across groups.Multivariate Cox regression was performed to evaluate prognostic factors,and a nomogram was constructed based on these results.Results:The OS and PFS of single-positive groups for CD38,CD138,CD45,CD56,and CD200 were all shorter than those of their respective single-negative groups(all P<0.05).Significant differences were observed in OS(P<0.001)and PFS(P=0.001)among Groups A,B,and C.Group A had shorter OS and PFS(all P=0.001)compared to the Group B+C(cases from Group B and Group C were combined).CD45 and CD200 double-positive was an independent prognostic factor for NDMM[hazard ratio(HR)=2.178,95%confidence interval(CI)1.048 to 4.529;P=0.037].The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance(concordance index=0.706;95%CI 0.661 to 0.751).Conclusion:NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS.Compared with the use of either marker alone,the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.
文摘The charge carrier transport and recombination dynamics in the quantum dots-based light-emitting diodes(QLEDs)featuring multiple emitting layers(M-EMLs)has a great impact on the device performance.In this work,QLEDs based on M-EMLs separated by polyethyleneimine ethoxylated(PEIE)layer with different stacking sequences of blue(B),green(G),and red(R)QDs layer were used to intuitively explore the injection,transportation and recombination processes of the charge carriers in QLEDs by using the time-resolved electroluminescence(TrEL)spectra.From the TrEL spectra mea-surements,green and red emissions were obtained first in the QLEDs with the EMLs sequences of G/PEIE/B/PEIE/R and B/PEIE/R/PEIE/G along the direction of light emission,respectively.While the QLEDs adopt EMLs sequences of B/PEIE/G/PEIE/R,the blue,green and red emissions were obtained nearly at the same time.The above phenomenon can be attributed to different charge carrier transmission and radiation recombination process in the EMLs due to different valence band offsets and conduction band offsets between R-,G-and B-QDs by using different sequences of EMLs.White emission with coordi-nates of(0.31,0.31)and correlated color temperature(CCT)of 5916 K was obtained in the QLEDs with the EMLs se-quences of B/PEIE/G/PEIE/R,which can be attributed to the relative uniform emission of B-,G-and R-QDs due to the effec-tive injection and radiation recombination of charge carriers in each of the EMLs.The above results have great significance for further understanding and improving the performance of QLEDs with M-EMLs.
基金supported in part by the National Natural Science Foundation of China(62173051)the Fundamental Research Funds for the Central Universities(2024CDJCGJ012,2023CDJXY-010)+1 种基金the Chongqing Technology Innovation and Application Development Special Key Project(CSTB2022TIADCUX0015,CSTB2022TIAD-KPX0162)the China Postdoctoral Science Foundation(2024M763865)
文摘Dear Editor,This letter addresses the impulse game problem for a general scope of deterministic,multi-player,nonzero-sum differential games wherein all participants adopt impulse controls.Our objective is to formulate this impulse game problem with the modified objective function including interaction costs among the players in a discontinuous fashion,and subsequently,to derive a verification theorem for identifying the feedback Nash equilibrium strategy.
文摘This paper introduces an optimized planning approach for integrating photovoltaic as distributed generation (PV-DG) into the radial distribution power systems, utilizing exhaustive load flow (ELF), loss sensitivity factor (LSF), genetic algorithms (GA) methods, and numerical method based on LSF. The methodology aims to determine the optimal allocation and sizing of multiple PV-DG to minimize power loss through time series power flow analysis. An approach utilizing continuous sensitivity analysis is developed and inherently leverages power flow and loss equations to compute LSF of all buses in the system towards employing a dynamic PV-DG model for more accurate results. The algorithm uses a numerical grid search method to optimize PV-DG placement in a power distribution system, focusing on minimizing system losses. It combines iterative analysis, sensitivity assessment, and comprehensive visualization to identify and present the optimal PV-DG configurations. The present-ed algorithms are verified through co-simulation framework combining MATLAB and OpenDSS to carry out analysis for 12-bus radial distribution test system. The proposed numerical method is compared with other algorithms, such as ELF, LSF methods, and Genetic Algorithms (GA). Results show that the proposed numerical method performs well in comparison with LSF and ELF solutions.
文摘Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesis remains unclear,the progress in multimodal imaging(MMI)has enhanced our understanding of MEWDS.Most cases of MEWDS are idiopathic,lacking a definite cause,and can spontaneously recover;these are what we term classic MEWDS.Consequently,MEWDS is often referred to as the“common cold of the retina”.Simultaneously,patients with other disorders may present with varying degrees of manifestations similar to MEWDS.The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment.These MEWDS-like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms.Thus,they differ from classic MEWDS in certain aspects.Using the keywords“MEWDSlike”and“Secondary MEWDS”,we searched for all relevant studies published in the PubMed database from January 2021 to January 2024.Subsequently,we retrospectively summarized the clinical and imaging characteristics of MEWDS,along with the manifestations in other diseases that resembled those of MEWDS,and compared classic MEWDS with these similar presentations.Based on our review,we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis.We recommend paying close attention to patients suspected of having MEWDS,as there may be more serious systemic or ocular disorders that require prompt treatment.
基金supported by grant from the National Natural Science Foundation of China(Grant No.82300231).
文摘Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金Private DonationLa Trobe Research Focus AreasMultiple Sclerosis Australia,Grant/Award Number:20-032。
文摘Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.
