[目的/意义]通过最大瓦解结构准确识别科学研究前沿中的关键节点并追踪其演化路径,为把握领域发展规律、优化科研资源配置提供支持,突破现有研究聚焦孤立节点的局部特征,以及难以捕捉知识网络中具有协同作用且对全局连通性有级联破坏力...[目的/意义]通过最大瓦解结构准确识别科学研究前沿中的关键节点并追踪其演化路径,为把握领域发展规律、优化科研资源配置提供支持,突破现有研究聚焦孤立节点的局部特征,以及难以捕捉知识网络中具有协同作用且对全局连通性有级联破坏力的关键节点集合的问题。[方法/过程]以量子通信领域为例,基于2015—2024年Web of Science的6538篇文献构建关键词共现网络,融合多中心性指标并利用熵权法评估节点重要性,采用贪心算法识别MDS,分析其功能协同特征与演化轨迹。[结果/结论]研究表明,MDS仅占网络规模的18%~22%,移除该集合后网络最大连通组件规模下降超过70%,效果显著优于传统方法。关键节点在功能上呈现“主题—方法—工具—目标”的互补协同结构,其演化路径清晰展示了量子通信从理论奠基、技术攻坚到应用落地的三阶段发展轨迹,验证了MDS框架的有效性和实用性。展开更多
在电力变压器中,绝缘油由于老化、过热、放电等原因不断劣化,并伴随H_(2)、CH_(4)、C_(2)H_(2)、C_(2)H_(4)、C_(2)H6等特征气体的产出,在油中发生不同程度的扩散。然而,由于气体结构和绝缘体系不同,天然气合成油(gas to liquid,GTL)中...在电力变压器中,绝缘油由于老化、过热、放电等原因不断劣化,并伴随H_(2)、CH_(4)、C_(2)H_(2)、C_(2)H_(4)、C_(2)H6等特征气体的产出,在油中发生不同程度的扩散。然而,由于气体结构和绝缘体系不同,天然气合成油(gas to liquid,GTL)中特征气体的扩散特征尚不明确,多气体分子之间的相互作用也不明晰。为揭示该扩散机理,文中利用分子动力学方法从微观层次上研究混合气体在静止GTL中的扩散行为。通过对比单一、二元、多元气体体系的扩散系数、运动轨迹、自由体积分数和相互作用能,分析混合气体加入对扩散的影响。结果表明,对于单一体系,气体在GTL中的扩散系数表现为:H_(2)>烃类气体,且烃类气体的扩散系数与分子质量成反比,不同气体的扩散符合“空穴跳跃扩散理论”。对于二元体系,混合气体中气体分子的扩散作用具有协同效应,具体表现为不同气体分子之间的斥力作用。同时,混合气体的加入使得CH_(4)和H_(2)的相互作用能分别降低9.21、3.76 kJ/mol;H_(2)和CH_(4)自由体积分数分别增加了27.5%和113.7%,进而增加气体运动空间,削弱GTL对气体的束缚作用,提高气体扩散系数。明确GTL油中气体扩散特征将有利于电力变压器的故障诊断。展开更多
Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fa...Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fast conductance velocity.This not only depends on axonal diameter and insulation by glial processes,but it requires the structural integrity of the axon.展开更多
The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves gl...The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.展开更多
Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, ...Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.展开更多
Ruscogenin,a steroidal sapogenin,is primarily derived from the genus Ruscus.It demonstrates a wide range of pharmacological actions that hold substantial promise for therapeutic use.By conducting a comprehensive exami...Ruscogenin,a steroidal sapogenin,is primarily derived from the genus Ruscus.It demonstrates a wide range of pharmacological actions that hold substantial promise for therapeutic use.By conducting a comprehensive examination of electronic databases including PubMed,ScienceDirect,and SciFinder,we identified studies on ruscogenin to date.This review aims at emphasizing the findings related to the bioactivities of ruscogenin,particularly its protective activities in neurological and inflammatory disorders,hemorrhoids,and cancer.Ruscogenin has been demonstrated to possess anti-ulcer,anti-osteoporotic,and skin-lightening properties as a therapeutic agent.It has also been proven effective in managing metabolic disorders by reducing inflammation and improving lipid metabolism,particularly in conditions such as non-alcoholic steatohepatitis and diabetic nephropathy.Reports indicate that it can prevent acute lung injury by protecting pulmonary endothelial cells from apoptosis and modulating inflammatory cytokines.Additionally,ruscogenin promotes neurological recovery by mitigating oxidative stress.It also shows anti-cancer properties,leading to apoptosis and hindering metastasis,particularly in pancreatic and hepatocellular carcinoma.This review summarizes the potential medical applications of ruscogenin and underscores the need for further research on its mechanisms of action.展开更多
This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to use...This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to user behavior and platform-driven moderation on social media.The proposed methodological framework(1)utilizes large language models for social media post analysis and categorization,(2)employs k-means clustering for content characterization,and(3)incorporates the TODIM(Tomada de Decisão Interativa Multicritério)method to determine moderation strategies based on expert judgments.In general,the fully integrated framework leverages the strengths of these intelligent systems in a more systematic evaluation of large-scale decision problems.When applied in social media moderation,this approach promotes nuanced and context-sensitive self-moderation by taking into account factors such as cultural background and geographic location.The application of this framework is demonstrated within Facebook groups.Eight distinct content clusters encompassing safety,harassment,diversity,and misinformation are identified.Analysis revealed a preference for content removal across all clusters,suggesting a cautious approach towards potentially harmful content.However,the framework also highlights the use of other moderation actions,like account suspension,depending on the content category.These findings contribute to the growing body of research on self-moderation and offer valuable insights for creating safer and more inclusive online spaces within smaller communities.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygiu...AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygium excision with either pentagonal(created by shaping the junction with the recipient conjunctiva into a wedge)or quadrangular conjunctival autograft transplantation.All patients completed a 6mo postoperative follow-up.The primary outcome measure was the incidence of graft retraction;secondary outcomes included graft displacement requiring re-suturing and pterygium recurrence rate.RESULTS:The study enrolled 58 participants,comprising 26(15 males,11 females)in the pentagonal graft group(mean age:54.9±13.1y),and 32(17 males,15 females)in the quadrangular graft group(mean age:57.6±10.4y).Graft retraction occurred in only 1 eye(3.8%)in the pentagonal autograft group,compared to 9 eyes(28.1%)in the quadrangular autograft group.No cases of graft displacement requiring re-suturing were reported in the pentagonal autograft group.Although graft displacement and recurrence requiring re-suturing were observed less frequently in surgeries with a pentagonal graft,the difference was not statistically significant(P>0.05).CONCLUSION:Designing the conjunctival autograft in a pentagonal shape—mimicking geodesic dome architecture and conforming to the eye’s spherical structure—enhances compatibility with the recipient conjunctiva and improves resistance to physical traction forces.This design effectively reduces the incidence of graft retraction and other related complications,providing a more favorable surgical option for pterygium treatment.展开更多
Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reti...Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.展开更多
Background:A significant challenge regarding notable historical figures is determining the accuracy of the words and actions attributed to them with the limited available evidence,when their biographers have presented...Background:A significant challenge regarding notable historical figures is determining the accuracy of the words and actions attributed to them with the limited available evidence,when their biographers have presented a biased life assessment.Lauded as a founding suffragette,the first female school principal,and the first white female practicing physician in Canada,Dr.Emily Stowe did not help historians.She destroyed her records,leaving her life story to be told by her daughter,who portrayed her as a heroine–a view that has persisted since the start of the 20th century.To improve the accuracy of assessing the life of Emily Stowe,as much information as possible about Stowe must be collected and interpreted.Methods:Presented is a narrative research method for analyzing historical figures that examines 22 life-changing events in the life of Stowe by answering six types of questions about each event:when,where,who,what,how,and why.Results:This narrative research,representing a psychoanalytic research process,finds that much of the repeated story of Stowe is either exaggerated or likely false.Conclusion:Following the example of Emily Stowe,this unique method is applicable for improving the historical accuracy in assessing the lives of other notable figures.It represents a method extendable to those currently alive,outside the public eye,searching to develop their own narrative.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
文摘[目的/意义]通过最大瓦解结构准确识别科学研究前沿中的关键节点并追踪其演化路径,为把握领域发展规律、优化科研资源配置提供支持,突破现有研究聚焦孤立节点的局部特征,以及难以捕捉知识网络中具有协同作用且对全局连通性有级联破坏力的关键节点集合的问题。[方法/过程]以量子通信领域为例,基于2015—2024年Web of Science的6538篇文献构建关键词共现网络,融合多中心性指标并利用熵权法评估节点重要性,采用贪心算法识别MDS,分析其功能协同特征与演化轨迹。[结果/结论]研究表明,MDS仅占网络规模的18%~22%,移除该集合后网络最大连通组件规模下降超过70%,效果显著优于传统方法。关键节点在功能上呈现“主题—方法—工具—目标”的互补协同结构,其演化路径清晰展示了量子通信从理论奠基、技术攻坚到应用落地的三阶段发展轨迹,验证了MDS框架的有效性和实用性。
文摘在电力变压器中,绝缘油由于老化、过热、放电等原因不断劣化,并伴随H_(2)、CH_(4)、C_(2)H_(2)、C_(2)H_(4)、C_(2)H6等特征气体的产出,在油中发生不同程度的扩散。然而,由于气体结构和绝缘体系不同,天然气合成油(gas to liquid,GTL)中特征气体的扩散特征尚不明确,多气体分子之间的相互作用也不明晰。为揭示该扩散机理,文中利用分子动力学方法从微观层次上研究混合气体在静止GTL中的扩散行为。通过对比单一、二元、多元气体体系的扩散系数、运动轨迹、自由体积分数和相互作用能,分析混合气体加入对扩散的影响。结果表明,对于单一体系,气体在GTL中的扩散系数表现为:H_(2)>烃类气体,且烃类气体的扩散系数与分子质量成反比,不同气体的扩散符合“空穴跳跃扩散理论”。对于二元体系,混合气体中气体分子的扩散作用具有协同效应,具体表现为不同气体分子之间的斥力作用。同时,混合气体的加入使得CH_(4)和H_(2)的相互作用能分别降低9.21、3.76 kJ/mol;H_(2)和CH_(4)自由体积分数分别增加了27.5%和113.7%,进而增加气体运动空间,削弱GTL对气体的束缚作用,提高气体扩散系数。明确GTL油中气体扩散特征将有利于电力变压器的故障诊断。
基金funded by a grant of the Deutsche Forschungsgemeinschaft(DFG)(SFB 1348,B5)to CK.
文摘Peripheral sensory neurons perceive external signals and convey signals to the central nervous system(CNS).Information transmission occurs via often extremely long axons and timely reactions of the animal require a fast conductance velocity.This not only depends on axonal diameter and insulation by glial processes,but it requires the structural integrity of the axon.
基金funded by the Alexander von Humboldt Stiftungsupported by DFG (SCH W534/6-1 to SWS)
文摘The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.
文摘Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.
文摘Ruscogenin,a steroidal sapogenin,is primarily derived from the genus Ruscus.It demonstrates a wide range of pharmacological actions that hold substantial promise for therapeutic use.By conducting a comprehensive examination of electronic databases including PubMed,ScienceDirect,and SciFinder,we identified studies on ruscogenin to date.This review aims at emphasizing the findings related to the bioactivities of ruscogenin,particularly its protective activities in neurological and inflammatory disorders,hemorrhoids,and cancer.Ruscogenin has been demonstrated to possess anti-ulcer,anti-osteoporotic,and skin-lightening properties as a therapeutic agent.It has also been proven effective in managing metabolic disorders by reducing inflammation and improving lipid metabolism,particularly in conditions such as non-alcoholic steatohepatitis and diabetic nephropathy.Reports indicate that it can prevent acute lung injury by protecting pulmonary endothelial cells from apoptosis and modulating inflammatory cytokines.Additionally,ruscogenin promotes neurological recovery by mitigating oxidative stress.It also shows anti-cancer properties,leading to apoptosis and hindering metastasis,particularly in pancreatic and hepatocellular carcinoma.This review summarizes the potential medical applications of ruscogenin and underscores the need for further research on its mechanisms of action.
基金funded by the Office of the Vice-President for Research and Development of Cebu Technological University.
文摘This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to user behavior and platform-driven moderation on social media.The proposed methodological framework(1)utilizes large language models for social media post analysis and categorization,(2)employs k-means clustering for content characterization,and(3)incorporates the TODIM(Tomada de Decisão Interativa Multicritério)method to determine moderation strategies based on expert judgments.In general,the fully integrated framework leverages the strengths of these intelligent systems in a more systematic evaluation of large-scale decision problems.When applied in social media moderation,this approach promotes nuanced and context-sensitive self-moderation by taking into account factors such as cultural background and geographic location.The application of this framework is demonstrated within Facebook groups.Eight distinct content clusters encompassing safety,harassment,diversity,and misinformation are identified.Analysis revealed a preference for content removal across all clusters,suggesting a cautious approach towards potentially harmful content.However,the framework also highlights the use of other moderation actions,like account suspension,depending on the content category.These findings contribute to the growing body of research on self-moderation and offer valuable insights for creating safer and more inclusive online spaces within smaller communities.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
文摘AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygium excision with either pentagonal(created by shaping the junction with the recipient conjunctiva into a wedge)or quadrangular conjunctival autograft transplantation.All patients completed a 6mo postoperative follow-up.The primary outcome measure was the incidence of graft retraction;secondary outcomes included graft displacement requiring re-suturing and pterygium recurrence rate.RESULTS:The study enrolled 58 participants,comprising 26(15 males,11 females)in the pentagonal graft group(mean age:54.9±13.1y),and 32(17 males,15 females)in the quadrangular graft group(mean age:57.6±10.4y).Graft retraction occurred in only 1 eye(3.8%)in the pentagonal autograft group,compared to 9 eyes(28.1%)in the quadrangular autograft group.No cases of graft displacement requiring re-suturing were reported in the pentagonal autograft group.Although graft displacement and recurrence requiring re-suturing were observed less frequently in surgeries with a pentagonal graft,the difference was not statistically significant(P>0.05).CONCLUSION:Designing the conjunctival autograft in a pentagonal shape—mimicking geodesic dome architecture and conforming to the eye’s spherical structure—enhances compatibility with the recipient conjunctiva and improves resistance to physical traction forces.This design effectively reduces the incidence of graft retraction and other related complications,providing a more favorable surgical option for pterygium treatment.
文摘Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.
文摘Background:A significant challenge regarding notable historical figures is determining the accuracy of the words and actions attributed to them with the limited available evidence,when their biographers have presented a biased life assessment.Lauded as a founding suffragette,the first female school principal,and the first white female practicing physician in Canada,Dr.Emily Stowe did not help historians.She destroyed her records,leaving her life story to be told by her daughter,who portrayed her as a heroine–a view that has persisted since the start of the 20th century.To improve the accuracy of assessing the life of Emily Stowe,as much information as possible about Stowe must be collected and interpreted.Methods:Presented is a narrative research method for analyzing historical figures that examines 22 life-changing events in the life of Stowe by answering six types of questions about each event:when,where,who,what,how,and why.Results:This narrative research,representing a psychoanalytic research process,finds that much of the repeated story of Stowe is either exaggerated or likely false.Conclusion:Following the example of Emily Stowe,this unique method is applicable for improving the historical accuracy in assessing the lives of other notable figures.It represents a method extendable to those currently alive,outside the public eye,searching to develop their own narrative.
文摘AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
