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
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
The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of ...The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of many cylindrical structures.Many active and passive control methods have been employed for the vibration suppression of an isolated cylinder undergoing vortex-induced vibrations(VIV).The FIV suppression methods are mainly extended to the multiple cylinders from the vibration control of the isolated cylinder.Due to the mutual interference between the multiple cylinders,the FIV mechanism is more complex than the VIV mechanism,which makes a great challenge for the FIV suppression.Some efforts have been devoted to vibration suppression of multiple cylinder systems undergoing FIV over the past two decades.The control methods,such as helical strakes,splitter plates,control rods and flexible sheets,are not always effective,depending on many influence factors,such as the spacing ratio,the arrangement geometrical shape,the flow velocity and the parameters of the vibration control devices.The FIV response,hydrodynamic features and wake patterns of the multiple cylinders equipped with vibration control devices are reviewed and summarized.The FIV suppression efficiency of the vibration control methods are analyzed and compared considering different influence factors.Further research on the FIV suppression of multiple cylinders is suggested to provide insight for the development of FIV control methods and promote engineering applications of FIV control methods.展开更多
Toeplitz matrix-vector multiplication is widely used in various fields,including optimal control,systolic finite field multipliers,multidimensional convolution,etc.In this paper,we first present a non-asymptotic quant...Toeplitz matrix-vector multiplication is widely used in various fields,including optimal control,systolic finite field multipliers,multidimensional convolution,etc.In this paper,we first present a non-asymptotic quantum algorithm for Toeplitz matrix-vector multiplication with time complexity O(κpolylogn),whereκand 2n are the condition number and the dimension of the circulant matrix extended from the Toeplitz matrix,respectively.For the case with an unknown generating function,we also give a corresponding non-asymptotic quantum version that eliminates the dependency on the L_(1)-normρof the displacement of the structured matrices.Due to the good use of the special properties of Toeplitz matrices,the proposed quantum algorithms are sufficiently accurate and efficient compared to the existing quantum algorithms under certain circumstances.展开更多
Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow d...Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.展开更多
●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features ...●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.展开更多
Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features...Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features of magnetic reconnection have been well developed and applied successfully to systems with symmetrical property,such as toroidal fusion plasmas and laboratory experiments with an axial symmetry.But in asymmetric systems,the 3D features are inevitably different from those in the 2D case.Magnetic reconnection structures in multiple celestial body systems,particularly star-planet-Moon systems,bring fresh insights to the understanding of the 3D geometry of reconnection.Thus,we take magnetic reconnection in an ancient solar-lunar terrestrial magneto-plasma system as an example by using its crucial parameters approximately estimated already and also some specific applications in pathways for energy and matter transports among Earth,ancient Moon,and the interplanetary magnetic field(IMF).Then,magnetic reconnection of the ancient lunar-terrestrial magnetospheres with the IMF is investigated numerically in this work.In a 3D simulation for the Earth-Moon-IMF system,topological features of complex magnetic reconnection configurations and dynamical characteristics of magnetic reconnection processes are studied.It is found that a coupled lunar-terrestrial magnetosphere is formed,and under various IMF orientations,multiple X-points emerge at distinct locations,showing three typical magnetic reconnection structures in such a geometry,i.e.,the X-line,the triple current sheets,and the A-B null pairs.The results can conduce to further understanding of reconnection physics in 3D for plasmas in complex magnetic configurations,and also a possible mechanism for energy and matters transport in evolutions of similar astrophysical systems.展开更多
Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complication...Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.展开更多
Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four R...Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.展开更多
Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X...Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X_(i)(s))^(2))^(1/2)(i=1,…,d)is commensurate with■for s=(s_(1),…,s_(N)),t=(t_(1),…,t_(N))∈R~N,α_(i)∈(0,1],and with the continuous functionγ(·)satisfying certain conditions.First,the upper and lower bounds of the hitting probabilities of X can be derived from the corresponding generalized Hausdorff measure and capacity,which are based on the kernel functions depending explicitly onγ(·).Furthermore,the multiple intersections of the sample paths of two independent centered space-time anisotropic Gaussian fields with different distributions are considered.Our results extend the corresponding results for anisotropic Gaussian fields to a large class of space-time anisotropic Gaussian fields.展开更多
BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal...BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.展开更多
Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we r...Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.展开更多
High-voltage circuit breakers are the core equipment in power networks,and to a certain extent,are related to the safe and reliable operation of power systems.However,their core components are prone to mechanical faul...High-voltage circuit breakers are the core equipment in power networks,and to a certain extent,are related to the safe and reliable operation of power systems.However,their core components are prone to mechanical faults.This study proposes a component separation method to detect multiple mechanical faults in circuit breakers that can achieve online real-time monitoring.First,a model and strategy are presented for obtaining mechanical voiceprint signals from circuit breakers.Subsequently,the component separation method was used to decompose the voiceprint signals of multiple faults into individual component signals.Based on this,the recognition of the features of a single-fault voiceprint signal can be achieved.Finally,multiple faults in high-voltage circuit breakers were identified through an experimental simulation and verification of the circuit breaker voiceprint signals collected from the substation site.The research results indicate that the proposed method exhibits excellent performance for multiple mechanical faults,such as spring structures and loose internal components of circuit breakers.In addition,it provides a reference method for the real-time online monitoring of high-voltage circuit breakers.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
In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and perfo...In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and performance evaluation.When the beam energy is low,the effect of multiple Coulomb scattering on the measured resolution of the Device Under Test(DUT)must be considered to accurately evaluate the performance of the pixel chips and detectors.This study aimed to investigate the effect of multiple Coulomb scattering on the measured resolution,particularly at low beam energies.Simulations were conducted using Allpix^(2) to study the effects of multiple Coulomb scattering under different beam energies,material budgets,and telescope layouts.The simulations also provided the minimum energy at which the effect of multiple Coulomb scattering could be ignored.Compared with the results of a five-layer detector system tested with an electron beam at DESY,the simulation results were consistent with the beam test results,confirming the reliability of the simulations.展开更多
In this paper,ambient IoT is used as a typical use case of massive connections for the sixth generation(6G)mobile communications where we derive the performance requirements to facilitate the evaluation of technical s...In this paper,ambient IoT is used as a typical use case of massive connections for the sixth generation(6G)mobile communications where we derive the performance requirements to facilitate the evaluation of technical solutions.A rather complete design of unsourced multiple access is proposed in which two key parts:a compressed sensing module for active user detection,and a sparse interleaver-division multiple access(SIDMA)module are simulated side by side on a same platform at balanced signal to noise ratio(SNR)operating points.With a proper combination of compressed sensing matrix,a convolutional encoder,receiver algorithms,the simulated performance results appear superior to the state-of-the-art benchmark,yet with relatively less complicated processing.展开更多
In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible ...In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.展开更多
Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traver...Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traversal and pseudorandomness. In this work, a novel five-dimensional(5D) Hamiltonian conservative hyperchaotic system is proposed based on the 5D Euler equation. The proposed system can have different types of coordinate transformations and time reversal symmetries. In this work, Hamilton energy and Casimir energy are analyzed firstly, and it is proved that the new system satisfies Hamilton energy conservation and can generate chaos. Then, the complex dynamic characteristics of the system are demonstrated and the conservatism and chaos characteristics of the system are verified through the correlation analysis methods such as phase diagram, equilibrium point, Lyapunov exponent, bifurcation diagram, and SE complexity. In addition, a detailed analysis of the multistable characteristics of the system reveals that many energy-related coexisting orbits exist. Based on the infinite number of center-type and saddle-type equilibrium points, the dynamic characteristics of the hidden multistability of the system are revealed. Then, the National Institute of Standards and Technology(NIST)test of the new system shows that the chaotic sequence generated by the system has strong pseudo-random. Finally, the circuit simulation and hardware circuit experiment of the system are carried out with Multisim simulation software and digital signal processor(DSP) respectively. The experimental results confirm that the new system has good ergodicity and realizability.展开更多
This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the at...This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the attacker and the capability to defend the GNSS during navigation countermeasures.Key evaluation indicators for the jamming effect of GNSS suppressive and deceptive jamming sources are first created,their evaluation models are built,and their detection procedures are sorted out,as the basis for determining the deployment principles.The principles for collaboratively deploying multi-jamming sources are developed to obtain the deployment structures(including the required number,structures in demand,and corresponding positions)of three single interference sources required by collaboratively deploying.Accordingly,simulation and hardware-in-loop testing results are presented to determine a rational configuration of the collaborative deployment of multi-jamming sources in the set situation and further realize the full-domain deployment of an interference network from ground,air to space.Varied evaluation indices for the deployment effect are finally developed to evaluate the deployment effect of the proposed configuration and further verify its reliability and rationality.展开更多
Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug r...Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.展开更多
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.
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.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U2106223,51979193,52301352)。
文摘The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of many cylindrical structures.Many active and passive control methods have been employed for the vibration suppression of an isolated cylinder undergoing vortex-induced vibrations(VIV).The FIV suppression methods are mainly extended to the multiple cylinders from the vibration control of the isolated cylinder.Due to the mutual interference between the multiple cylinders,the FIV mechanism is more complex than the VIV mechanism,which makes a great challenge for the FIV suppression.Some efforts have been devoted to vibration suppression of multiple cylinder systems undergoing FIV over the past two decades.The control methods,such as helical strakes,splitter plates,control rods and flexible sheets,are not always effective,depending on many influence factors,such as the spacing ratio,the arrangement geometrical shape,the flow velocity and the parameters of the vibration control devices.The FIV response,hydrodynamic features and wake patterns of the multiple cylinders equipped with vibration control devices are reviewed and summarized.The FIV suppression efficiency of the vibration control methods are analyzed and compared considering different influence factors.Further research on the FIV suppression of multiple cylinders is suggested to provide insight for the development of FIV control methods and promote engineering applications of FIV control methods.
基金supported by the National Natural Science Foundation of China(Grant Nos.62071015 and 62171264)。
文摘Toeplitz matrix-vector multiplication is widely used in various fields,including optimal control,systolic finite field multipliers,multidimensional convolution,etc.In this paper,we first present a non-asymptotic quantum algorithm for Toeplitz matrix-vector multiplication with time complexity O(κpolylogn),whereκand 2n are the condition number and the dimension of the circulant matrix extended from the Toeplitz matrix,respectively.For the case with an unknown generating function,we also give a corresponding non-asymptotic quantum version that eliminates the dependency on the L_(1)-normρof the displacement of the structured matrices.Due to the good use of the special properties of Toeplitz matrices,the proposed quantum algorithms are sufficiently accurate and efficient compared to the existing quantum algorithms under certain circumstances.
文摘Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.
基金Supported by the National Natural Science Foundation of China(No.82171073No.82101147).
文摘●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11975087,42261134533,and 42011530086)the National Magnetic Confinement Fusion Energy Research and Development Program of China(Grant No.2022YFE03190400)the Heilongjiang Touyan Innovation Team Program,China.
文摘Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features of magnetic reconnection have been well developed and applied successfully to systems with symmetrical property,such as toroidal fusion plasmas and laboratory experiments with an axial symmetry.But in asymmetric systems,the 3D features are inevitably different from those in the 2D case.Magnetic reconnection structures in multiple celestial body systems,particularly star-planet-Moon systems,bring fresh insights to the understanding of the 3D geometry of reconnection.Thus,we take magnetic reconnection in an ancient solar-lunar terrestrial magneto-plasma system as an example by using its crucial parameters approximately estimated already and also some specific applications in pathways for energy and matter transports among Earth,ancient Moon,and the interplanetary magnetic field(IMF).Then,magnetic reconnection of the ancient lunar-terrestrial magnetospheres with the IMF is investigated numerically in this work.In a 3D simulation for the Earth-Moon-IMF system,topological features of complex magnetic reconnection configurations and dynamical characteristics of magnetic reconnection processes are studied.It is found that a coupled lunar-terrestrial magnetosphere is formed,and under various IMF orientations,multiple X-points emerge at distinct locations,showing three typical magnetic reconnection structures in such a geometry,i.e.,the X-line,the triple current sheets,and the A-B null pairs.The results can conduce to further understanding of reconnection physics in 3D for plasmas in complex magnetic configurations,and also a possible mechanism for energy and matters transport in evolutions of similar astrophysical systems.
文摘Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.
基金supported by Incubation Program for Clinical Trials(No.19HXFH030)Achievement Transformation Project(No.CGZH21001)+4 种基金1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)Translational Research Grant of NCRCH(No.2021WWB03),Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2023HXBH111)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603).
文摘Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.
基金supported by the National Natural Science Foundation of China(12371150,11971432)the Natural Science Foundation of Zhejiang Province(LY21G010003)+2 种基金the Management Project of"Digital+"Discipline Construction of Zhejiang Gongshang University(SZJ2022A012,SZJ2022B017)the Characteristic&Preponderant Discipline of Key Construction Universities in Zhejiang Province(Zhejiang Gongshang University-Statistics)the Scientific Research Projects of Universities in Anhui Province(2022AH050955)。
文摘Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X_(i)(s))^(2))^(1/2)(i=1,…,d)is commensurate with■for s=(s_(1),…,s_(N)),t=(t_(1),…,t_(N))∈R~N,α_(i)∈(0,1],and with the continuous functionγ(·)satisfying certain conditions.First,the upper and lower bounds of the hitting probabilities of X can be derived from the corresponding generalized Hausdorff measure and capacity,which are based on the kernel functions depending explicitly onγ(·).Furthermore,the multiple intersections of the sample paths of two independent centered space-time anisotropic Gaussian fields with different distributions are considered.Our results extend the corresponding results for anisotropic Gaussian fields to a large class of space-time anisotropic Gaussian fields.
文摘BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.
基金This study is supported by the National Key Research and Development Program of China(2017YFB0307500).
文摘Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.
基金supported by the State Key Laboratory of Technology and Equipment for Defense against Power System Operational Risks(No.SGNR0000KJJS2302137)the National Natural Science Foundation of China(Grant No.62203248)the Natural Science Foundation of Shandong Province(Grant No.ZR2020ME194).
文摘High-voltage circuit breakers are the core equipment in power networks,and to a certain extent,are related to the safe and reliable operation of power systems.However,their core components are prone to mechanical faults.This study proposes a component separation method to detect multiple mechanical faults in circuit breakers that can achieve online real-time monitoring.First,a model and strategy are presented for obtaining mechanical voiceprint signals from circuit breakers.Subsequently,the component separation method was used to decompose the voiceprint signals of multiple faults into individual component signals.Based on this,the recognition of the features of a single-fault voiceprint signal can be achieved.Finally,multiple faults in high-voltage circuit breakers were identified through an experimental simulation and verification of the circuit breaker voiceprint signals collected from the substation site.The research results indicate that the proposed method exhibits excellent performance for multiple mechanical faults,such as spring structures and loose internal components of circuit breakers.In addition,it provides a reference method for the real-time online monitoring of high-voltage circuit breakers.
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 the National Natural Science Foundation of China(Nos.11875274 and U1232202)。
文摘In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and performance evaluation.When the beam energy is low,the effect of multiple Coulomb scattering on the measured resolution of the Device Under Test(DUT)must be considered to accurately evaluate the performance of the pixel chips and detectors.This study aimed to investigate the effect of multiple Coulomb scattering on the measured resolution,particularly at low beam energies.Simulations were conducted using Allpix^(2) to study the effects of multiple Coulomb scattering under different beam energies,material budgets,and telescope layouts.The simulations also provided the minimum energy at which the effect of multiple Coulomb scattering could be ignored.Compared with the results of a five-layer detector system tested with an electron beam at DESY,the simulation results were consistent with the beam test results,confirming the reliability of the simulations.
文摘In this paper,ambient IoT is used as a typical use case of massive connections for the sixth generation(6G)mobile communications where we derive the performance requirements to facilitate the evaluation of technical solutions.A rather complete design of unsourced multiple access is proposed in which two key parts:a compressed sensing module for active user detection,and a sparse interleaver-division multiple access(SIDMA)module are simulated side by side on a same platform at balanced signal to noise ratio(SNR)operating points.With a proper combination of compressed sensing matrix,a convolutional encoder,receiver algorithms,the simulated performance results appear superior to the state-of-the-art benchmark,yet with relatively less complicated processing.
文摘In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.
基金Project supported by the Heilongjiang Province Natural Science Foundation Joint Guidance Project,China (Grant No.LH2020F022)the Fundamental Research Funds for the Central Universities,China (Grant No.3072022CF0801)。
文摘Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traversal and pseudorandomness. In this work, a novel five-dimensional(5D) Hamiltonian conservative hyperchaotic system is proposed based on the 5D Euler equation. The proposed system can have different types of coordinate transformations and time reversal symmetries. In this work, Hamilton energy and Casimir energy are analyzed firstly, and it is proved that the new system satisfies Hamilton energy conservation and can generate chaos. Then, the complex dynamic characteristics of the system are demonstrated and the conservatism and chaos characteristics of the system are verified through the correlation analysis methods such as phase diagram, equilibrium point, Lyapunov exponent, bifurcation diagram, and SE complexity. In addition, a detailed analysis of the multistable characteristics of the system reveals that many energy-related coexisting orbits exist. Based on the infinite number of center-type and saddle-type equilibrium points, the dynamic characteristics of the hidden multistability of the system are revealed. Then, the National Institute of Standards and Technology(NIST)test of the new system shows that the chaotic sequence generated by the system has strong pseudo-random. Finally, the circuit simulation and hardware circuit experiment of the system are carried out with Multisim simulation software and digital signal processor(DSP) respectively. The experimental results confirm that the new system has good ergodicity and realizability.
基金the National Natural Science Foundation of China(Grant No.42174047 and No.42174036)the National Science Foundation Project for Outstanding Youth(No.42104034).
文摘This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the attacker and the capability to defend the GNSS during navigation countermeasures.Key evaluation indicators for the jamming effect of GNSS suppressive and deceptive jamming sources are first created,their evaluation models are built,and their detection procedures are sorted out,as the basis for determining the deployment principles.The principles for collaboratively deploying multi-jamming sources are developed to obtain the deployment structures(including the required number,structures in demand,and corresponding positions)of three single interference sources required by collaboratively deploying.Accordingly,simulation and hardware-in-loop testing results are presented to determine a rational configuration of the collaborative deployment of multi-jamming sources in the set situation and further realize the full-domain deployment of an interference network from ground,air to space.Varied evaluation indices for the deployment effect are finally developed to evaluate the deployment effect of the proposed configuration and further verify its reliability and rationality.
基金Research Projects-Joint Fund for Applied Basic Research of Kunming Medical University,Yunnan Provincial Department of Science and Technology(No.2018FE001(-113),No.202301AY070001-098)Open project of Yunnan Clinical Medical Center(Nos.2020LCZXKF-XY02,XY06,XY16+1 种基金2022LCZXKF-XY02)Yunnan Health Training Project of High Level Talents(No.D–2018018).
文摘Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.