Recently, many bit commitment schemes have been presented. This paper presents a new practical bit commitment scheme based on Schnorr's one-time knowledge proof scheme,where the use of cut-and-choose method and ma...Recently, many bit commitment schemes have been presented. This paper presents a new practical bit commitment scheme based on Schnorr's one-time knowledge proof scheme,where the use of cut-and-choose method and many random exam candidates in the protocols are replaced by a single challenge number. Therefore the proposed bit commitment scheme is more efficient and practical than the previous schemes In addition, the security of the proposed scheme under factoring assumption is proved, thus the cryptographic basis of the proposed scheme is clarified.展开更多
Factoring quadratics over Z is a staple of introductory algebra and textbooks tend to create the impression that doable factorizations are fairly common. To the contrary, if coefficients of a general quadratic are sel...Factoring quadratics over Z is a staple of introductory algebra and textbooks tend to create the impression that doable factorizations are fairly common. To the contrary, if coefficients of a general quadratic are selected randomly without restriction, the probability that a factorization exists is zero. We achieve a specific quantification of the probability of factoring quadratics by taking a new approach that considers the absolute size of coefficients to be a parameter n. This restriction allows us to make relative likelihood estimates based on finite sample spaces. Our probability estimates are then conditioned on the size parameter n and the behavior of the conditional estimates may be studied as the parameter is varied. Specifically, we enumerate how many formal factored expressions could possibly correspond to a quadratic for a given size parameter. The conditional probability of factorization as a function of n is just the ratio of this enumeration to the total number of possible quadratics consistent with n. This approach is patterned after the well-known case where factorizations are carried out over a finite field. We review the finite field method as background for our method of dealing with Z [x]. The monic case is developed independently of the general case because it is simpler and the resulting probability estimating formula is more accurate. We conclude with a comparison of our theoretical probability estimates with exact data generated by a computer search for factorable quadratics corresponding to various parameter values.展开更多
Objective Focusing on the s ecurity problem of authentication and confidentiality in the context of computer networks, a digital signature scheme was proposed based on the public key crypt osystem. Methods Firstly...Objective Focusing on the s ecurity problem of authentication and confidentiality in the context of computer networks, a digital signature scheme was proposed based on the public key crypt osystem. Methods Firstly, the course of digital signature based on the public key cryptosystem was given. Then, RSA and ELGamal schemes were de scribed respectively. They were the basis of the proposed scheme. Generalized EL Gamal type signature schemes were listed. After comparing with each other, one s cheme, whose Signature equation was (m+r)x=j+s modΦ(p) , was adopted in the des igning. Results Based on two well-known cryptographic assumpti ons, the factorization and the discrete logarithms, a digital signature scheme w as presented. It must be required that s' was not equal to p'q' in the signing p rocedure, because attackers could forge the signatures with high probabilities i f the discrete logarithms modulo a large prime were solvable. The variable publi c key “e” is used instead of the invariable parameter “3” in Harn's signatu re scheme to enhance the security. One generalized ELGamal type scheme made the proposed scheme escape one multiplicative inverse operation in the signing proce dure and one modular exponentiation in the verification procedure. Concl usion The presented scheme obtains the security that Harn's scheme was originally claimed. It is secure if the factorization and the discrete logarithm s are simultaneously unsolvable.展开更多
It is an open problem if an elementary p-group of rank k ≥ 3 does admit full-rank normalized factorization into two of its subsets such that one of the factors has p elements. The paper provides an answer in the p ≤...It is an open problem if an elementary p-group of rank k ≥ 3 does admit full-rank normalized factorization into two of its subsets such that one of the factors has p elements. The paper provides an answer in the p ≤ 7 special case.展开更多
In order to answer a question motivated by constructing substitution boxes in block ciphers we will exhibit an infinite family of full-rank factorizations of elementary 2-groups into two factors having equal sizes.
This paper proposes three new attacks. In the first attack we consider the class of the public exponents satisfying an equation e X-N Y ＋（ap^r＋ bq^r）Y = Z for suitably small positive integers a, b. Applying contin...This paper proposes three new attacks. In the first attack we consider the class of the public exponents satisfying an equation e X-N Y ＋（ap^r＋ bq^r）Y = Z for suitably small positive integers a, b. Applying continued fractions we show thatY/Xcan be recovered among the convergents of the continued fraction expansion of e/N. Moreover, we show that the number of such exponents is at least N^（2/（r＋1）-ε）where ε≥ 0 is arbitrarily small for large N. The second and third attacks works upon k RSA public keys（N_i, e_i） when there exist k relations of the form e_ix-N_iy_i ＋（ap_i^r ＋ bq_i^r ）y_i = z_i or of the form e_ix_i-N_iy ＋（ap_i^r ＋ bq_i^r ）y = z_i and the parameters x, x_i, y, y_i, z_i are suitably small in terms of the prime factors of the moduli. We apply the LLL algorithm, and show that our strategy enables us to simultaneously factor k prime power RSA moduli.展开更多
The hardness of the integer factoring problem(IFP)plays a core role in the security of RSA-like cryptosystems that are widely used today.Besides Shor’s quantum algorithm that can solve IFP within polynomial time,quan...The hardness of the integer factoring problem(IFP)plays a core role in the security of RSA-like cryptosystems that are widely used today.Besides Shor’s quantum algorithm that can solve IFP within polynomial time,quantum annealing algorithms(QAA)also manifest certain advantages in factoring integers.In experimental aspects,the reported integers that were successfully factored by using the D-wave QAA platform are much larger than those being factored by using Shor-like quantum algorithms.In this paper,we report some interesting observations about the effects of QAA for solving IFP.More specifically,we introduce a metric,called T-factor that measures the density of occupied qubits to some extent when conducting IFP tasks by using D-wave.We find that T-factor has obvious effects on annealing times for IFP:The larger of T-factor,the quicker of annealing speed.The explanation of this phenomenon is also given.展开更多
Integer factorization (IFP), also called prime factorization, is an important problem in number theory, cryptography, and quantum computation. Factoring large integers to attack the RSA cryptosystem is intractable for...Integer factorization (IFP), also called prime factorization, is an important problem in number theory, cryptography, and quantum computation. Factoring large integers to attack the RSA cryptosystem is intractable for powerful supercomputers, let alone classical computers. In 1994, Shor [1]presented an algorithm that potentially enabled a quantum computer to find prime factors in polynomial time.展开更多
This paper presents a factoring algorithm for computing source-to- K terminal (SKT) reliability, the probability that a source s can send message to a specified set of terminals K, in acyclic directed networks (AD-net...This paper presents a factoring algorithm for computing source-to- K terminal (SKT) reliability, the probability that a source s can send message to a specified set of terminals K, in acyclic directed networks (AD-networks) in which both nodes and edges can fail. Based on Pivotal decomposition theorem, a new formula is derived for computing the SKT reliability of AD-networks. By establishing a topological property of AD-networks, it is shown that the SKT reliability of AD- networks can be computed by recursively applying this formula. Two new Reliability- Preserving Reductions are also introduced. The recursion tree generated by the presented algorithm has at most 2 leaf nodes, where V and K are the numbers of nodes and terminals, respectively, while C is the number of the nodes satisfying some specified conditions. The computation complexity of the new algorithm is O (E. V. 2) in the worst case, where E is the number of edges. For source-to-all-terminal (SAT) reliability, its computation complexity is O(E). Comparison of the new algorithm with the existing ones indicates that the new algorithm is more efficient for computing the SKT reliability of AD-networks.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Let D=pq be the product of two distinct odd primes.Assuming the parity conjecture,we construct infinitely many r≥1 such that E2rD:y2=x3-2rDx has conjectural rank one and vp(x([k]Q))≠vq(x([k]Q))for any odd integer k,...Let D=pq be the product of two distinct odd primes.Assuming the parity conjecture,we construct infinitely many r≥1 such that E2rD:y2=x3-2rDx has conjectural rank one and vp(x([k]Q))≠vq(x([k]Q))for any odd integer k,where Q is the generator of the free part of E(Q).Furthermore,under the generalized Riemann hypothesis,the minimal value of r is less than c log4 D for some absolute constant c.As a corollary,one can factor D by computing the generator Q.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,end...For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good m...Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.展开更多
The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiqui...The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.展开更多
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
基金Supported by the National Natural Science Foundation of China(No.69772035,69882002) and "863" Programme
文摘Recently, many bit commitment schemes have been presented. This paper presents a new practical bit commitment scheme based on Schnorr's one-time knowledge proof scheme,where the use of cut-and-choose method and many random exam candidates in the protocols are replaced by a single challenge number. Therefore the proposed bit commitment scheme is more efficient and practical than the previous schemes In addition, the security of the proposed scheme under factoring assumption is proved, thus the cryptographic basis of the proposed scheme is clarified.
文摘Factoring quadratics over Z is a staple of introductory algebra and textbooks tend to create the impression that doable factorizations are fairly common. To the contrary, if coefficients of a general quadratic are selected randomly without restriction, the probability that a factorization exists is zero. We achieve a specific quantification of the probability of factoring quadratics by taking a new approach that considers the absolute size of coefficients to be a parameter n. This restriction allows us to make relative likelihood estimates based on finite sample spaces. Our probability estimates are then conditioned on the size parameter n and the behavior of the conditional estimates may be studied as the parameter is varied. Specifically, we enumerate how many formal factored expressions could possibly correspond to a quadratic for a given size parameter. The conditional probability of factorization as a function of n is just the ratio of this enumeration to the total number of possible quadratics consistent with n. This approach is patterned after the well-known case where factorizations are carried out over a finite field. We review the finite field method as background for our method of dealing with Z [x]. The monic case is developed independently of the general case because it is simpler and the resulting probability estimating formula is more accurate. We conclude with a comparison of our theoretical probability estimates with exact data generated by a computer search for factorable quadratics corresponding to various parameter values.
文摘Objective Focusing on the s ecurity problem of authentication and confidentiality in the context of computer networks, a digital signature scheme was proposed based on the public key crypt osystem. Methods Firstly, the course of digital signature based on the public key cryptosystem was given. Then, RSA and ELGamal schemes were de scribed respectively. They were the basis of the proposed scheme. Generalized EL Gamal type signature schemes were listed. After comparing with each other, one s cheme, whose Signature equation was (m+r)x=j+s modΦ(p) , was adopted in the des igning. Results Based on two well-known cryptographic assumpti ons, the factorization and the discrete logarithms, a digital signature scheme w as presented. It must be required that s' was not equal to p'q' in the signing p rocedure, because attackers could forge the signatures with high probabilities i f the discrete logarithms modulo a large prime were solvable. The variable publi c key “e” is used instead of the invariable parameter “3” in Harn's signatu re scheme to enhance the security. One generalized ELGamal type scheme made the proposed scheme escape one multiplicative inverse operation in the signing proce dure and one modular exponentiation in the verification procedure. Concl usion The presented scheme obtains the security that Harn's scheme was originally claimed. It is secure if the factorization and the discrete logarithm s are simultaneously unsolvable.
文摘It is an open problem if an elementary p-group of rank k ≥ 3 does admit full-rank normalized factorization into two of its subsets such that one of the factors has p elements. The paper provides an answer in the p ≤ 7 special case.
文摘In order to answer a question motivated by constructing substitution boxes in block ciphers we will exhibit an infinite family of full-rank factorizations of elementary 2-groups into two factors having equal sizes.
文摘This paper proposes three new attacks. In the first attack we consider the class of the public exponents satisfying an equation e X-N Y ＋（ap^r＋ bq^r）Y = Z for suitably small positive integers a, b. Applying continued fractions we show thatY/Xcan be recovered among the convergents of the continued fraction expansion of e/N. Moreover, we show that the number of such exponents is at least N^（2/（r＋1）-ε）where ε≥ 0 is arbitrarily small for large N. The second and third attacks works upon k RSA public keys（N_i, e_i） when there exist k relations of the form e_ix-N_iy_i ＋（ap_i^r ＋ bq_i^r ）y_i = z_i or of the form e_ix_i-N_iy ＋（ap_i^r ＋ bq_i^r ）y = z_i and the parameters x, x_i, y, y_i, z_i are suitably small in terms of the prime factors of the moduli. We apply the LLL algorithm, and show that our strategy enables us to simultaneously factor k prime power RSA moduli.
基金the National Natural Science Foundation of China(NSFC)(Grant No.61972050)the Open Foundation of StateKey Laboratory ofNetworking and Switching Technology(Beijing University of Posts and Telecommunications)(SKLNST-2020-2-16).
文摘The hardness of the integer factoring problem(IFP)plays a core role in the security of RSA-like cryptosystems that are widely used today.Besides Shor’s quantum algorithm that can solve IFP within polynomial time,quantum annealing algorithms(QAA)also manifest certain advantages in factoring integers.In experimental aspects,the reported integers that were successfully factored by using the D-wave QAA platform are much larger than those being factored by using Shor-like quantum algorithms.In this paper,we report some interesting observations about the effects of QAA for solving IFP.More specifically,we introduce a metric,called T-factor that measures the density of occupied qubits to some extent when conducting IFP tasks by using D-wave.We find that T-factor has obvious effects on annealing times for IFP:The larger of T-factor,the quicker of annealing speed.The explanation of this phenomenon is also given.
文摘Integer factorization (IFP), also called prime factorization, is an important problem in number theory, cryptography, and quantum computation. Factoring large integers to attack the RSA cryptosystem is intractable for powerful supercomputers, let alone classical computers. In 1994, Shor [1]presented an algorithm that potentially enabled a quantum computer to find prime factors in polynomial time.
文摘This paper presents a factoring algorithm for computing source-to- K terminal (SKT) reliability, the probability that a source s can send message to a specified set of terminals K, in acyclic directed networks (AD-networks) in which both nodes and edges can fail. Based on Pivotal decomposition theorem, a new formula is derived for computing the SKT reliability of AD-networks. By establishing a topological property of AD-networks, it is shown that the SKT reliability of AD- networks can be computed by recursively applying this formula. Two new Reliability- Preserving Reductions are also introduced. The recursion tree generated by the presented algorithm has at most 2 leaf nodes, where V and K are the numbers of nodes and terminals, respectively, while C is the number of the nodes satisfying some specified conditions. The computation complexity of the new algorithm is O (E. V. 2) in the worst case, where E is the number of edges. For source-to-all-terminal (SAT) reliability, its computation complexity is O(E). Comparison of the new algorithm with the existing ones indicates that the new algorithm is more efficient for computing the SKT reliability of AD-networks.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by National Natural Science Foundation of China (Grant No. 11271212)
文摘Let D=pq be the product of two distinct odd primes.Assuming the parity conjecture,we construct infinitely many r≥1 such that E2rD:y2=x3-2rDx has conjectural rank one and vp(x([k]Q))≠vq(x([k]Q))for any odd integer k,where Q is the generator of the free part of E(Q).Furthermore,under the generalized Riemann hypothesis,the minimal value of r is less than c log4 D for some absolute constant c.As a corollary,one can factor D by computing the generator Q.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
基金funded by the Science and Technology Research of Henan Province,No.242103810041(to JY)。
文摘For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
基金supported by the Medicine-Engineering Interdisciplinary Project of Sun Yat-sen Memorial Hospital,China,No.YXYGRH202203(to YW)Key-Area Research and Development Program of Guangdong Province,China,No.2023B1111050003(to HC)Guangzhou Science and Technology Talent Project of China,No.201909020006(to HC).
文摘Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.
基金supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province,China,No.2022ZQNZD01010010the National Natural Science Foundation of China,No.82371390Fujian Province Scientific Foundation,No.2023J01725(all to XC).
文摘The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
