A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H n X = 1. In this easel K is called a complement of H in G. In this note some results on complem...A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H n X = 1. In this easel K is called a complement of H in G. In this note some results on complemented subgroups of finite groups are obtained.展开更多
In this paper, we have proved that for a relatively complemented distributive lattice L,there exists one and only one completion ? of L such that for every ξ∈?, there exists afamily {S_α}_(α∈△) of non-vacuous su...In this paper, we have proved that for a relatively complemented distributive lattice L,there exists one and only one completion ? of L such that for every ξ∈?, there exists afamily {S_α}_(α∈△) of non-vacuous subsets of L satisfying ξ= ∨[∧f(S_α)]. Such a completion? is called the entire completion of L. We have in this paper extended the homomorphic extension theorem of a generalizedBoolean lattice to that of a relatively complemented distributive lattice and proved that the lat-tice of the congruences on a relatively complemented distributive lattice is isomorphicwith the lattice of the convex sublattices containing a fixed element and that the entire comple-tion of a relatively complemented distributive lattice L, the lattice of the completable con-gruences on L and the lattice of the completable convex sublattices of L containing a fixed ele-ment are isomorphic.展开更多
We extend the notions of commutativity,ideals,anisotropy,and complemented subtriples of Jordan triple systems to those of Jordan quadruple systems.We show that if S is a complemented subsystem of an anisotropic commut...We extend the notions of commutativity,ideals,anisotropy,and complemented subtriples of Jordan triple systems to those of Jordan quadruple systems.We show that if S is a complemented subsystem of an anisotropic commutative Jordan quadruple system U,then S and its annihilator S^(⊥)are orthogonal ideals and U=S⊕S^(⊥).We also prove that the range of a structural projection on an anisotropic commutative Jordan quadruple system is a complemented ideal and,conversely,a complemented subsystem of an anisotropic commutative Jordan quadruple system is the range of a unique structural projection.展开更多
Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience...Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.展开更多
Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in comp...BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.展开更多
Assume G is a finite group and H a subgroup of G. If there exists a subgroup K of G such that G = HK and H ∩ K = 1, then K is said to be a complement to H in G. A finite p-group G is called an NC-group if all its pro...Assume G is a finite group and H a subgroup of G. If there exists a subgroup K of G such that G = HK and H ∩ K = 1, then K is said to be a complement to H in G. A finite p-group G is called an NC-group if all its proper normal subgroups not contained in de（G） have complements. In this paper, some properties of NC-groups are investigated and some classes of NC-groups are classified. Keywords Finite p-groups, normal subgroups, subgroup complement展开更多
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery...Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.展开更多
The complement system is crucial for maintaining immunological homeostasis in the liver,playing a significant role in both innate and adaptive immune responses.Dysregulation of this system is closely linked to the pat...The complement system is crucial for maintaining immunological homeostasis in the liver,playing a significant role in both innate and adaptive immune responses.Dysregulation of this system is closely linked to the pathogenesis of various liver diseases.Modulating the complement system can affect the progression of these conditions.To provide insights into treating liver injury by targeting the regu-lation of the complement system,we conducted a comprehensive search of major biomedical databases,including MEDLINE,PubMed,EMBASE,and Web of Science,to identify articles on complement and liver injury and reviewed the functions and mechanisms of the complement system in liver injury.展开更多
Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which...Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and H...BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.展开更多
Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomeruloneph...Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.展开更多
We deal with the properties of incompressible and pairwise incompressible surfaces in knot complements through the application of relevant properties of almost simple topological graphs.We analyze the topological grap...We deal with the properties of incompressible and pairwise incompressible surfaces in knot complements through the application of relevant properties of almost simple topological graphs.We analyze the topological graph invariants associated with surfaces embedded in the complements of alternating and almost alternating knots.Specifically,we prove that the characteristic numbers of these graphs remain invariant under two fundamental transformations(R-move and S^(2)-move).Leveraging the interplay between characteristic numbers and Euler characteristics,and further connecting Euler characteristics to surface genus,we derive novel results regarding the genus of incompressible pairwise incompressible surfaces.Additionally,we establish a discriminant criterion to determine when such surfaces in knot complements admit genus zero.展开更多
Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identifi...Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identified that C3 is primarily derived from periodontal fibroblasts.Subsequently,we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis.C3ar−/−mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice,characterized by mild gingival tissue damage and reduced alveolar bone loss.This reduction was associated with decreased production of proinflammatory mediators and reduced osteoclast infiltration in the periodontal tissues.Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation.Finally,by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis,we found that the results observed in mice were consistent with human data.Therefore,our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis,driven by macrophage M1 polarization and osteoclast differentiation.These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.展开更多
BACKGROUND C3 glomerulopathies(C3G)are a rare cause of kidney failure resulting from complement dysregulation.Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation.Treatment e...BACKGROUND C3 glomerulopathies(C3G)are a rare cause of kidney failure resulting from complement dysregulation.Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation.Treatment efficacy in this setting with eculizumab,a terminal complement inhibitor,is largely unknown.AIM To determine the outcomes of kidney transplantation in patients with C3G and the potential impact of eculizumab.METHODS We retrospectively studied kidney transplant recipients who underwent a post-transplant biopsy confirming C3G between January 1,1993 and December 31,2023 at a single center.Only the first episode of kidney transplant was reviewed.The electronic medical records were reviewed for post-transplant allograft function,indication for biopsy,time to biopsy from transplant,time to allograft failure from transplantation,post-C3G treatment,complement laboratory testing,and concurrent malignancy/infection.Reports,and when available slides and immunofluorescence/electron microscopic images,were re-reviewed by a renal pathologist.RESULTS A total of fifteen patients were included in this study.Fourteen patients had suspected recurrent disease,with a pre-transplant native kidney report of C3G.One patient developed de novo C3G.Median post kidney transplant clinical follow up time was 91 months.Median time to recurrence was 7 months with median graft survival of 48 months post kidney transplantation.The most common index biopsy pattern of injury was endocapillary prolif-erative glomerulonephritis(often with exudative features)with or without mesangial hypercellularity(56%)followed by membranoproliferative glomerulonephritis(25%).Most patients developed membranoproliferative glomerulonephritis pattern of injury on follow up biopsies(63%).Seven patients with recurrent disease received treatment with eculizumab with a median graft survival of 73 months,with five functioning grafts by the end of the study period.Seven patients with recurrent disease did not receive therapy,and all lost their graft with a median graft survival of 22 months(P=0.003).CONCLUSION C3G following kidney transplantation is mostly a recurrent disorder with a poor prognosis in untreated patients.Untreated recurrence has a poor prognosis with median allograft survival<2 years.Early treatment with eculizumab may improve transplant outcomes in patients with recurrent C3G.展开更多
To integrate different renewable energy resources effectively in a microgrid, a configuration optimization model of a multi-energy distributed generation（DG） system and its auxiliary equipment is proposed. The model...To integrate different renewable energy resources effectively in a microgrid, a configuration optimization model of a multi-energy distributed generation（DG） system and its auxiliary equipment is proposed. The model mainly consists of two parts, the determination of initial configuration schemes according to user preference and the selection of the optimal scheme. The comprehensive evaluation index（CEI）, which is acquired through the analytic hierarchy process（AHP） weight calculation method, is adopted as the evaluation criterion to rank the initial schemes. The optimal scheme is obtained according to the ranking results. The proposed model takes the diversity of different equipment parameters and investment cost into consideration and can give relatively suitable and economical suggestions for system configuration.Additionally, unlike Homer Pro, the proposed model considers the complementation of different renewable energy resources, and thus the rationality of the multi-energy DG system is improved compared with the single evaluation criterion method which only considers the total cost.展开更多
The bimodulus material is a classical model to describe the elastic behavior of materials with tension-compression asymmetry.Due to the inherently nonlinear properties of bimodular materials,traditional iteration meth...The bimodulus material is a classical model to describe the elastic behavior of materials with tension-compression asymmetry.Due to the inherently nonlinear properties of bimodular materials,traditional iteration methods suffer from low convergence efficiency and poor adaptability for large-scale structures in engineering.In this paper,a novel 3D algorithm is established by complementing the three shear moduli of the constitutive equation in principal stress coordinates.In contrast to the existing 3D shear modulus constructed based on experience,in this paper the shear modulus is derived theoretically through a limit process.Then,a theoretically self-consistent complemented algorithm is established and implemented in ABAQUS via UMAT;its good stability and convergence efficiency are verified by using benchmark examples.Numerical analysis shows that the calculation error for bimodulus structures using the traditional linear elastic theory is large,which is not in line with reality.展开更多
基金Project supported by the National Natural Science Foundation of China (No.19671073) and theYouth Science Foundation of Shanxi
文摘A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H n X = 1. In this easel K is called a complement of H in G. In this note some results on complemented subgroups of finite groups are obtained.
文摘In this paper, we have proved that for a relatively complemented distributive lattice L,there exists one and only one completion ? of L such that for every ξ∈?, there exists afamily {S_α}_(α∈△) of non-vacuous subsets of L satisfying ξ= ∨[∧f(S_α)]. Such a completion? is called the entire completion of L. We have in this paper extended the homomorphic extension theorem of a generalizedBoolean lattice to that of a relatively complemented distributive lattice and proved that the lat-tice of the congruences on a relatively complemented distributive lattice is isomorphicwith the lattice of the convex sublattices containing a fixed element and that the entire comple-tion of a relatively complemented distributive lattice L, the lattice of the completable con-gruences on L and the lattice of the completable convex sublattices of L containing a fixed ele-ment are isomorphic.
文摘We extend the notions of commutativity,ideals,anisotropy,and complemented subtriples of Jordan triple systems to those of Jordan quadruple systems.We show that if S is a complemented subsystem of an anisotropic commutative Jordan quadruple system U,then S and its annihilator S^(⊥)are orthogonal ideals and U=S⊕S^(⊥).We also prove that the range of a structural projection on an anisotropic commutative Jordan quadruple system is a complemented ideal and,conversely,a complemented subsystem of an anisotropic commutative Jordan quadruple system is the range of a unique structural projection.
基金supported by the National Natural Science Foundation of China,No.31760290,82160688the Key Development Areas Project of Ganzhou Science and Technology,No.2022B-SF9554(all to XL)。
文摘Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
文摘BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.
基金Supported by National Natural Science Foundation of China(Grant Nos.11471198,11501045 and 11371232)
文摘Assume G is a finite group and H a subgroup of G. If there exists a subgroup K of G such that G = HK and H ∩ K = 1, then K is said to be a complement to H in G. A finite p-group G is called an NC-group if all its proper normal subgroups not contained in de（G） have complements. In this paper, some properties of NC-groups are investigated and some classes of NC-groups are classified. Keywords Finite p-groups, normal subgroups, subgroup complement
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
基金supported by the Department of Veterans Affairs(VA Merit Award BX004256)(to AMA)Emory Department of Neurosurgery Catalyst GrantEmory Medical Care Foundation Grant(to AMA and JG)。
文摘Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.
基金Supported by the Science and Technology Planning Projects of Guizhou Province,No.QKHJC-ZK[2022]YB642the Science and Technology Planning Projects of Zunyi City,No.ZSKHHZ(2022)344+4 种基金the WBE Liver Fibrosis Foundation,No.CFHPC2025028the Chinese Foundation for Hepatitis Prevention and Control Muxin Research Fund of CHB,No.MX202404Beijing Liver and Gallbladder Mutual Aid Public Welfare Foundation Artificial Liver Special Fund,No.iGandanF-1082024-Rgg018the Graduate Research Fund Project of Zunyi Medical University,No.ZYK246the Student Innovation and Entrepreneurship Training Program of Zunyi Medical University,No.2024106610923 and No.S202310661028.
文摘The complement system is crucial for maintaining immunological homeostasis in the liver,playing a significant role in both innate and adaptive immune responses.Dysregulation of this system is closely linked to the pathogenesis of various liver diseases.Modulating the complement system can affect the progression of these conditions.To provide insights into treating liver injury by targeting the regu-lation of the complement system,we conducted a comprehensive search of major biomedical databases,including MEDLINE,PubMed,EMBASE,and Web of Science,to identify articles on complement and liver injury and reviewed the functions and mechanisms of the complement system in liver injury.
文摘Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.
基金Supported by The Research Foundation of Jiangsu Province Administration of Traditional Chinese Medicine,No.MS2023088The Science and Technology Project of Changzhou,No.CE20225040+1 种基金The Research Foundation of Nanjing Medical University Changzhou Medical Center,No.CMCC202311Leading Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZLJ021.
文摘BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.
文摘Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.
基金Supported by the National Natural Science Foundation of China(Grant No.12026411)。
文摘We deal with the properties of incompressible and pairwise incompressible surfaces in knot complements through the application of relevant properties of almost simple topological graphs.We analyze the topological graph invariants associated with surfaces embedded in the complements of alternating and almost alternating knots.Specifically,we prove that the characteristic numbers of these graphs remain invariant under two fundamental transformations(R-move and S^(2)-move).Leveraging the interplay between characteristic numbers and Euler characteristics,and further connecting Euler characteristics to surface genus,we derive novel results regarding the genus of incompressible pairwise incompressible surfaces.Additionally,we establish a discriminant criterion to determine when such surfaces in knot complements admit genus zero.
基金supported by the National Key R&D Program of China(No.2022YFC2504200)the National Natural Science Foundation of China(Nos.82370936,81920108012,82471032).
文摘Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identified that C3 is primarily derived from periodontal fibroblasts.Subsequently,we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis.C3ar−/−mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice,characterized by mild gingival tissue damage and reduced alveolar bone loss.This reduction was associated with decreased production of proinflammatory mediators and reduced osteoclast infiltration in the periodontal tissues.Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation.Finally,by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis,we found that the results observed in mice were consistent with human data.Therefore,our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis,driven by macrophage M1 polarization and osteoclast differentiation.These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
文摘BACKGROUND C3 glomerulopathies(C3G)are a rare cause of kidney failure resulting from complement dysregulation.Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation.Treatment efficacy in this setting with eculizumab,a terminal complement inhibitor,is largely unknown.AIM To determine the outcomes of kidney transplantation in patients with C3G and the potential impact of eculizumab.METHODS We retrospectively studied kidney transplant recipients who underwent a post-transplant biopsy confirming C3G between January 1,1993 and December 31,2023 at a single center.Only the first episode of kidney transplant was reviewed.The electronic medical records were reviewed for post-transplant allograft function,indication for biopsy,time to biopsy from transplant,time to allograft failure from transplantation,post-C3G treatment,complement laboratory testing,and concurrent malignancy/infection.Reports,and when available slides and immunofluorescence/electron microscopic images,were re-reviewed by a renal pathologist.RESULTS A total of fifteen patients were included in this study.Fourteen patients had suspected recurrent disease,with a pre-transplant native kidney report of C3G.One patient developed de novo C3G.Median post kidney transplant clinical follow up time was 91 months.Median time to recurrence was 7 months with median graft survival of 48 months post kidney transplantation.The most common index biopsy pattern of injury was endocapillary prolif-erative glomerulonephritis(often with exudative features)with or without mesangial hypercellularity(56%)followed by membranoproliferative glomerulonephritis(25%).Most patients developed membranoproliferative glomerulonephritis pattern of injury on follow up biopsies(63%).Seven patients with recurrent disease received treatment with eculizumab with a median graft survival of 73 months,with five functioning grafts by the end of the study period.Seven patients with recurrent disease did not receive therapy,and all lost their graft with a median graft survival of 22 months(P=0.003).CONCLUSION C3G following kidney transplantation is mostly a recurrent disorder with a poor prognosis in untreated patients.Untreated recurrence has a poor prognosis with median allograft survival<2 years.Early treatment with eculizumab may improve transplant outcomes in patients with recurrent C3G.
基金The National Natural Science Foundation of China(No.51377021)the Science and Technology Project of State Grid Corporation of China(No.SGTJDK00DWJS1600014)
文摘To integrate different renewable energy resources effectively in a microgrid, a configuration optimization model of a multi-energy distributed generation（DG） system and its auxiliary equipment is proposed. The model mainly consists of two parts, the determination of initial configuration schemes according to user preference and the selection of the optimal scheme. The comprehensive evaluation index（CEI）, which is acquired through the analytic hierarchy process（AHP） weight calculation method, is adopted as the evaluation criterion to rank the initial schemes. The optimal scheme is obtained according to the ranking results. The proposed model takes the diversity of different equipment parameters and investment cost into consideration and can give relatively suitable and economical suggestions for system configuration.Additionally, unlike Homer Pro, the proposed model considers the complementation of different renewable energy resources, and thus the rationality of the multi-energy DG system is improved compared with the single evaluation criterion method which only considers the total cost.
基金the National Natural Science Foundation of China(Grant 51908071)Scientific Research Project of Education Department of Hunan Province(Grant 18C0194)Open Fund of Key Laboratory of Road Structure and Material of Ministry of Transport,Changsha University of Science&Technology(Grant kfi 170303).
文摘The bimodulus material is a classical model to describe the elastic behavior of materials with tension-compression asymmetry.Due to the inherently nonlinear properties of bimodular materials,traditional iteration methods suffer from low convergence efficiency and poor adaptability for large-scale structures in engineering.In this paper,a novel 3D algorithm is established by complementing the three shear moduli of the constitutive equation in principal stress coordinates.In contrast to the existing 3D shear modulus constructed based on experience,in this paper the shear modulus is derived theoretically through a limit process.Then,a theoretically self-consistent complemented algorithm is established and implemented in ABAQUS via UMAT;its good stability and convergence efficiency are verified by using benchmark examples.Numerical analysis shows that the calculation error for bimodulus structures using the traditional linear elastic theory is large,which is not in line with reality.
