As the power system transitions to a new green and low-carbon paradigm,the penetration of renewable energy in China’s power system is gradually increasing.However,the variability and uncertainty of renewable energy o...As the power system transitions to a new green and low-carbon paradigm,the penetration of renewable energy in China’s power system is gradually increasing.However,the variability and uncertainty of renewable energy output limit its profitability in the electricity market and hinder its market-based integration.This paper first constructs a wind-solar-thermalmulti-energy complementary system,analyzes its external game relationships,and develops a bi-level market optimization model.Then,it considers the contribution levels of internal participants to establish a comprehensive internal distribution evaluation index system.Finally,simulation studies using the IEEE 30-bus system demonstrate that the multi-energy complementary system stabilizes nodal outputs,enhances the profitability of market participants,and promotes the market-based integration of renewable energy.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
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
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
Under the current long-term electricity market mechanism,new energy and thermal power face issues such as deviation assessment and compression of generation space.The profitability of market players is limited.Simulta...Under the current long-term electricity market mechanism,new energy and thermal power face issues such as deviation assessment and compression of generation space.The profitability of market players is limited.Simultaneously,the cooperation model among various energy sources will have a direct impact on the alliance’s revenue and the equity of income distribution within the alliance.Therefore,integrating new energy with thermal power units into an integrated multi-energy complementary system to participate in the long-term electricity market holds significant potential.To simulate and evaluate the benefits and internal distribution methods of a multi-energy complementary system participating in long-term market transactions,this paper first constructs a multi-energy complementary system integrated with new energy and thermal power generation units at the same connection point,and participates in the annual bilateral game as a unified market entity to obtain the revenue value under the annual bilateral market.Secondly,based on the entropy weight method,improvements are made to the traditional Shapley value distribution model,and an internal distribution model for multi-energy complementary systems with multiple participants is constructed.Finally,a Markov Decision Process(MDP)evaluation system is constructed for practical case verification.The research results show that the improved Shapley value distribution model achieves higher satisfaction,providing a reasonable allocation scheme for multi-energy complementary cooperation models.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
Omsk hemorrhagic fever virus(OHFV) is a tick-borne flavivirus classified as a biosafety level-4(BSL4) pathogen. Studies of OHFV are restricted to be conducted within BSL4 laboratories. Currently, no commercial vaccine...Omsk hemorrhagic fever virus(OHFV) is a tick-borne flavivirus classified as a biosafety level-4(BSL4) pathogen. Studies of OHFV are restricted to be conducted within BSL4 laboratories. Currently, no commercial vaccines or antiviral drugs are available against OHFV infection. In this study, we recovered a replication-deficient OHFV with an NS1 deletion(OHFVDNS1) and reporter virus replacing NS1 with the Gaussia luciferase(Gluc)(OHFV-ΔNS1-Gluc). Both the defective OHFVDNS1 and OHFV-ΔNS1-Gluc virus could only replicate efficiently in the BHK21 cell line expressing NS1(BHK21NS1) but not in na?ve BHK21 cells. The Gluc reporter gene of OHFV-ΔNS1-Gluc virus was maintained stably after serial passaging of BHK21NS1 cells and was used to surrogate the replication of OHFV. Using NITD008, OHFV-ΔNS1-Gluc virus was validated for antiviral screening, and high-throughput screening parameters were optimized in a 96-well plate format with a calculated Z0 value above 0.5. The OHFV-ΔNS1-Gluc reporter virus is a powerful tool for antiviral screening as well as viral replication and pathogenesis studies in BSL2 laboratories.展开更多
Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of va...Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs.Therefore,to achieve a transplantable organ in animals without rejection,creation of vascular endothelial cells derived from humans within the organ is necessary.In this study,to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals,we generated rat-mouse chimeras by injection of rat embryonic stem cells(rESCs)into mouse blastocysts with deficiency of Flk-1 protein,which is associated with endothelial and hematopoietic cell development.We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras.The whole yolk sac(YS)of Flk-1^EGFP/ECFP rat-mouse chimera was full of rat blood vasculature.Rat genes related to vascular endothelial cells,arteries,and veins,blood vessels formation process,as well as hematopoietic cells,were highly expressed in the YS.Our results suggested that rat vascular endothelial cells could undergo proliferation,migration,and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells,T cells,and myeloid cells in rat-mouse chimeras,which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse.展开更多
To optimize peaking operation when high proportion new energy accesses to power grid,evaluation indexes are proposed which simultaneously consider wind-solar complementation and source-load coupling.A typical wind-sol...To optimize peaking operation when high proportion new energy accesses to power grid,evaluation indexes are proposed which simultaneously consider wind-solar complementation and source-load coupling.A typical wind-solar power output scene model based on peaking demand is established which has anti-peaking characteristic.This model uses balancing scenes and key scenes with probability distribution based on improved Latin hypercube sampling(LHS)algorithm and scene reduction technology to illustrate the influence of wind-solar on peaking demand.Based on this,a peak shaving operation optimization model of high proportion new energy power generation is established.The various operating indexes after optimization in multi-scene peaking are calculated,and the ability of power grid peaking operation is compared whth that considering wind-solar complementation and source-load coupling.Finally,a case of high proportion new energy verifies the feasibility and validity of the proposed operation strategy.展开更多
In the background of the large-scale development and utilization of renewable energy,the joint operation of a variety of heterogeneous energy sources has become an inevitable development trend.However,the physical cha...In the background of the large-scale development and utilization of renewable energy,the joint operation of a variety of heterogeneous energy sources has become an inevitable development trend.However,the physical characteristics of different power sources and the inherent uncertainties of renewable energy power generation have brought difficulties to the planning,operation and control of power systems.For now,the utilization of multi-energy complementarity to promote energy transformation and improve the consumption of renewable energy has become a common understanding among researchers and the engineering community.This paper makes a review of the research on complementarity of new energy high proportion multi-energy systems from uncertainty modeling,complementary characteristics,planning and operation.We summarize the characteristics of the existing research and provide a reference for the further work.展开更多
BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury re...BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.AIM To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.METHODS A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury.C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment.We detected the effects of C2-FH on liver function,inflammatory response and complement activation.Additionally,RNA-sequencing(RNA-Seq)analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.RESULTS C2-FH inhibited the increase in serum alanine aminotransferase activity,aspartate aminotransferase activity and lactate dehydrogenase,and reduced liver tissue necrosis caused by APAP.Moreover,it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury.RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.CONCLUSION C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.展开更多
The multi-energy complementary distributed energy system (MCDES) covers a variety of energy forms, involves complex operation modes, and contains a wealth of control equipment and coupling links. It can realize the co...The multi-energy complementary distributed energy system (MCDES) covers a variety of energy forms, involves complex operation modes, and contains a wealth of control equipment and coupling links. It can realize the complementary and efficient use of different types of energy, which is the basic component of the physical layer of the Energy Internet. In this paper, aiming at the demand of the energy application for towns, a distributed energy system based on multi-energy complementary is constructed. Firstly, the supply condition of the distributed energy for the demonstration project is analyzed, and the architecture of the multi-energy complementary distributed energy system is established. Then the regulation strategy of the multi-energy complementary distributed energy system is proposed. Finally, an overall system scheme for the multi-energy complementary distributed energy system suitable for towns is developed, which provides a solid foundation for the development and promotion of the multi-energy complementary distributed energy system.展开更多
AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cel...AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.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
H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are prote...H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.展开更多
BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the rela...BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.RESULTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,P<0.001),CD59(RR=2.86,95%CI:1.36-6.01,P=0.005),and component 1(C1)(RR=5.88,95%CI:1.75-19.73,P=0.004)and serum levels of C3(standardized mean difference=1.82,95%CI:0.06-3.58,P=0.040)were significantly elevated in patients with CRC compared to healthy controls.Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis,whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression(P<0.05 for all).Although specific pooled results demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasizing the potential significance of monitoring elevated complement component levels.展开更多
BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor microenvironment.However,the exact underlying regulatory mechanisms remain unclear.AIM To investigate immune infiltration-...BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor microenvironment.However,the exact underlying regulatory mechanisms remain unclear.AIM To investigate immune infiltration-related differentially expressed genes(DEGs)in CC and specifically explored the role and potential molecular mechanisms of complement factor I(CFI).METHODS Immune infiltration-associated DEGs were screened for CC using bioinformatics.Quantitative reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell lines.Stable CFI-knockdown HT29 and HCT116 cell lines were constructed,and the diverse roles of CFI in vitro were assessed using CCK-8,5-ethynyl-2’-deoxyuridine,wound healing,and transwell assays.Hematoxylin and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude mice.Key proteins associated with glycolysis and the Wnt pathway were measured using western blotting.RESULTS Six key immune infiltration-related DEGs were screened,among which the expression of CFI,complement factor B,lymphoid enhancer binding factor 1,and SRY-related high-mobility-group box 4 was upregulated,whereas that of fatty acid-binding protein 1,and bone morphogenic protein-2 was downregulated.Furthermore,CFI could be used as a diagnostic biomarker for CC.Functionally,CFI silencing inhibited CC cell proliferation,migration,invasion,and tumor growth.Mechanistically,CFI knockdown downregulated the expression of key glycolysis-related proteins(glucose transporter type 1,hexokinase 2,lactate dehydrogenase A,and pyruvate kinase M2)and the Wnt pathway-related proteins(β-catenin and c-Myc).Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc pathway.CONCLUSION The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing glycolysis and the Wnt/β-catenin/c-Myc pathway,indicating that it could serve as a promising target for therapeutic intervention in CC.展开更多
基金funded by the National Key R&D Program of China,grant number 2019YFB1505400.
文摘As the power system transitions to a new green and low-carbon paradigm,the penetration of renewable energy in China’s power system is gradually increasing.However,the variability and uncertainty of renewable energy output limit its profitability in the electricity market and hinder its market-based integration.This paper first constructs a wind-solar-thermalmulti-energy complementary system,analyzes its external game relationships,and develops a bi-level market optimization model.Then,it considers the contribution levels of internal participants to establish a comprehensive internal distribution evaluation index system.Finally,simulation studies using the IEEE 30-bus system demonstrate that the multi-energy complementary system stabilizes nodal outputs,enhances the profitability of market participants,and promotes the market-based integration of renewable energy.
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.
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.
文摘Under the current long-term electricity market mechanism,new energy and thermal power face issues such as deviation assessment and compression of generation space.The profitability of market players is limited.Simultaneously,the cooperation model among various energy sources will have a direct impact on the alliance’s revenue and the equity of income distribution within the alliance.Therefore,integrating new energy with thermal power units into an integrated multi-energy complementary system to participate in the long-term electricity market holds significant potential.To simulate and evaluate the benefits and internal distribution methods of a multi-energy complementary system participating in long-term market transactions,this paper first constructs a multi-energy complementary system integrated with new energy and thermal power generation units at the same connection point,and participates in the annual bilateral game as a unified market entity to obtain the revenue value under the annual bilateral market.Secondly,based on the entropy weight method,improvements are made to the traditional Shapley value distribution model,and an internal distribution model for multi-energy complementary systems with multiple participants is constructed.Finally,a Markov Decision Process(MDP)evaluation system is constructed for practical case verification.The research results show that the improved Shapley value distribution model achieves higher satisfaction,providing a reasonable allocation scheme for multi-energy complementary cooperation models.
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 National Science and Technology Major Project on Important Infectious Diseases Prevention and Control (2018ZX10734404-010)National Key Research and Development Program of China (2018YFA0507201)
文摘Omsk hemorrhagic fever virus(OHFV) is a tick-borne flavivirus classified as a biosafety level-4(BSL4) pathogen. Studies of OHFV are restricted to be conducted within BSL4 laboratories. Currently, no commercial vaccines or antiviral drugs are available against OHFV infection. In this study, we recovered a replication-deficient OHFV with an NS1 deletion(OHFVDNS1) and reporter virus replacing NS1 with the Gaussia luciferase(Gluc)(OHFV-ΔNS1-Gluc). Both the defective OHFVDNS1 and OHFV-ΔNS1-Gluc virus could only replicate efficiently in the BHK21 cell line expressing NS1(BHK21NS1) but not in na?ve BHK21 cells. The Gluc reporter gene of OHFV-ΔNS1-Gluc virus was maintained stably after serial passaging of BHK21NS1 cells and was used to surrogate the replication of OHFV. Using NITD008, OHFV-ΔNS1-Gluc virus was validated for antiviral screening, and high-throughput screening parameters were optimized in a 96-well plate format with a calculated Z0 value above 0.5. The OHFV-ΔNS1-Gluc reporter virus is a powerful tool for antiviral screening as well as viral replication and pathogenesis studies in BSL2 laboratories.
基金financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030503)National Key Research and Development Program of China(2017YFA0105103)+5 种基金Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104004)Science and Technology Planning Project of Guangdong Province,China(2014A030312001,2017B020231001,2017A050501059,2017B030314056)Science and Technology Program of Guangzhou,China(201704030034)Research Unit of Generation of Large Animal Disease Models,Chinese Academy of Medical Sciences(2019-I2M-5-025)the Science and Technology Planning Project of Jiangmen(2017TD02)the Young People Fund of Wuyi University(2019TD05)。
文摘Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs.Therefore,to achieve a transplantable organ in animals without rejection,creation of vascular endothelial cells derived from humans within the organ is necessary.In this study,to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals,we generated rat-mouse chimeras by injection of rat embryonic stem cells(rESCs)into mouse blastocysts with deficiency of Flk-1 protein,which is associated with endothelial and hematopoietic cell development.We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras.The whole yolk sac(YS)of Flk-1^EGFP/ECFP rat-mouse chimera was full of rat blood vasculature.Rat genes related to vascular endothelial cells,arteries,and veins,blood vessels formation process,as well as hematopoietic cells,were highly expressed in the YS.Our results suggested that rat vascular endothelial cells could undergo proliferation,migration,and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells,T cells,and myeloid cells in rat-mouse chimeras,which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse.
基金Youth Science and Technology Fund Project of Gansu Province(No.18JR3RA011)Major Projects in Gansu Province(No.17ZD2GA010)+1 种基金Science and Technology Projects Funding of State Grid Corporation(No.522727160001)Science and Technology Projects of State Grid Gansu Electric Power Company(No.52272716000K)
文摘To optimize peaking operation when high proportion new energy accesses to power grid,evaluation indexes are proposed which simultaneously consider wind-solar complementation and source-load coupling.A typical wind-solar power output scene model based on peaking demand is established which has anti-peaking characteristic.This model uses balancing scenes and key scenes with probability distribution based on improved Latin hypercube sampling(LHS)algorithm and scene reduction technology to illustrate the influence of wind-solar on peaking demand.Based on this,a peak shaving operation optimization model of high proportion new energy power generation is established.The various operating indexes after optimization in multi-scene peaking are calculated,and the ability of power grid peaking operation is compared whth that considering wind-solar complementation and source-load coupling.Finally,a case of high proportion new energy verifies the feasibility and validity of the proposed operation strategy.
基金supported by the Science and Technology Project of State Grid Corporation of China.
文摘In the background of the large-scale development and utilization of renewable energy,the joint operation of a variety of heterogeneous energy sources has become an inevitable development trend.However,the physical characteristics of different power sources and the inherent uncertainties of renewable energy power generation have brought difficulties to the planning,operation and control of power systems.For now,the utilization of multi-energy complementarity to promote energy transformation and improve the consumption of renewable energy has become a common understanding among researchers and the engineering community.This paper makes a review of the research on complementarity of new energy high proportion multi-energy systems from uncertainty modeling,complementary characteristics,planning and operation.We summarize the characteristics of the existing research and provide a reference for the further work.
基金Supported by Natural Science Foundation of Guangxi,No.2020GXNSFDA238006Special Fund of the Central Government Guiding Local Scientific and Technological Development by Guangxi Science and Technology Department,No.GuikeZY21195024Research Enhancement Project for Junior Faculty in Higher Education Institutes of Guangxi,No.2018KY0419.
文摘BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.AIM To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.METHODS A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury.C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment.We detected the effects of C2-FH on liver function,inflammatory response and complement activation.Additionally,RNA-sequencing(RNA-Seq)analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.RESULTS C2-FH inhibited the increase in serum alanine aminotransferase activity,aspartate aminotransferase activity and lactate dehydrogenase,and reduced liver tissue necrosis caused by APAP.Moreover,it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury.RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.CONCLUSION C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.
文摘The multi-energy complementary distributed energy system (MCDES) covers a variety of energy forms, involves complex operation modes, and contains a wealth of control equipment and coupling links. It can realize the complementary and efficient use of different types of energy, which is the basic component of the physical layer of the Energy Internet. In this paper, aiming at the demand of the energy application for towns, a distributed energy system based on multi-energy complementary is constructed. Firstly, the supply condition of the distributed energy for the demonstration project is analyzed, and the architecture of the multi-energy complementary distributed energy system is established. Then the regulation strategy of the multi-energy complementary distributed energy system is proposed. Finally, an overall system scheme for the multi-energy complementary distributed energy system suitable for towns is developed, which provides a solid foundation for the development and promotion of the multi-energy complementary distributed energy system.
基金Supported by National Natural Sciences Foundation of China,No. 81001067the Ministry of Science and Technology International Cooperation Project, No. 2010DFA31870the AstraZeneca Special Research Foundation for Targeted Therapy of the Wu Jieping Medical Foundation, No. 320.6700.09068
文摘AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.
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supported by the earmarked fund for China Agriculture Research System(CARS-40)the Key Research and Development Project of Yangzhou(Modern Agriculture),China(YZ2022052)the‘‘High-end Talent Support Program’’of Yangzhou University,China。
文摘H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.
文摘BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.RESULTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,P<0.001),CD59(RR=2.86,95%CI:1.36-6.01,P=0.005),and component 1(C1)(RR=5.88,95%CI:1.75-19.73,P=0.004)and serum levels of C3(standardized mean difference=1.82,95%CI:0.06-3.58,P=0.040)were significantly elevated in patients with CRC compared to healthy controls.Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis,whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression(P<0.05 for all).Although specific pooled results demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasizing the potential significance of monitoring elevated complement component levels.
文摘BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor microenvironment.However,the exact underlying regulatory mechanisms remain unclear.AIM To investigate immune infiltration-related differentially expressed genes(DEGs)in CC and specifically explored the role and potential molecular mechanisms of complement factor I(CFI).METHODS Immune infiltration-associated DEGs were screened for CC using bioinformatics.Quantitative reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell lines.Stable CFI-knockdown HT29 and HCT116 cell lines were constructed,and the diverse roles of CFI in vitro were assessed using CCK-8,5-ethynyl-2’-deoxyuridine,wound healing,and transwell assays.Hematoxylin and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude mice.Key proteins associated with glycolysis and the Wnt pathway were measured using western blotting.RESULTS Six key immune infiltration-related DEGs were screened,among which the expression of CFI,complement factor B,lymphoid enhancer binding factor 1,and SRY-related high-mobility-group box 4 was upregulated,whereas that of fatty acid-binding protein 1,and bone morphogenic protein-2 was downregulated.Furthermore,CFI could be used as a diagnostic biomarker for CC.Functionally,CFI silencing inhibited CC cell proliferation,migration,invasion,and tumor growth.Mechanistically,CFI knockdown downregulated the expression of key glycolysis-related proteins(glucose transporter type 1,hexokinase 2,lactate dehydrogenase A,and pyruvate kinase M2)and the Wnt pathway-related proteins(β-catenin and c-Myc).Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc pathway.CONCLUSION The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing glycolysis and the Wnt/β-catenin/c-Myc pathway,indicating that it could serve as a promising target for therapeutic intervention in CC.
