Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice

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.

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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.

Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system

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.

Association of complement components with risk of colorectal cancer:A systematic review and meta-analysis

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.

Complement factor Ⅰ knockdown inhibits colon cancer development by affecting Wnt/β-catenin/c-Myc signaling pathway and glycolysis

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.

Tumor-related factor complement Clq/TNF-related protein 6 affects the development of digestive system tumors through the phosphatidylinositol 3-kinase pathway

In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.

Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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.

Interleukin-1 receptor associated kinase 2 is a functional downstream regulator of complement factor D that controls mitochondrial fitness in diabetic cardiomyopathy

Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in the pathogenesis of the disease and its progression towards heart failure,including endothelial dysfunction,autonomic neuropathy,metabolic alterations,oxidative stress,and alterations in ion homeostasis,especially calcium transients[1].In Military Medical Research,Jiang et al.[2]sought to determine the functional role of complement factor D(Adipsin)in the pathophysiology of diabetic cardiomyopathy.

宽负荷下切圆燃煤锅炉H_(2)S分布特性的数值模拟

锅炉采用空气分级燃烧降低NO_(x)排放的同时也提高了主燃区H_(2)S体积分数。炉墙壁面过高的H_(2)S体积分数是加剧水冷壁高温腐蚀的重要因素。为保障新能源并网发电,大型燃煤机组灵活调峰的需求增加,不同负荷下的水冷壁近壁面H_(2)S分布特性值得关注。通过正交试验分析了切圆燃煤锅炉运行参数对水冷壁近壁面H_(2)S体积分数分布的影响。选取一台超临界600 MW切圆燃煤锅炉建立数值模型,设计L_(16)(4^(5))正交工况,覆盖100%BMCR、75%THA,50%THA以及35%BMCR四种负荷。建立了自定义SO_(x)生成模型以确定燃料硫的析出和转化路径,模型包含多表面反应子模型以描述焦炭与O_(2)/CO_(2)/H_(2)O等3种气体的异相反应,并确定焦炭气化反应消耗量占总消耗量的比例,进而对炉膛H_(2)S空间分布进行了模拟计算。研究表明,近壁面高体积分数H_(2)S区域主要位于投运燃烧器层中最下层燃烧器以下以及最上层燃烧器以上至SOFA层之间,烟气切圆沿炉膛高度增加逐渐增大是造成后一区域H_(2)S体积分数较高的重要原因。35%BMCR负荷下水冷壁重点区域的H_(2)S平均体积分数为364μL/L,明显低于其他负荷。锅炉运行参数对重点区域H_(2)S体积分数影响程度的排序为:锅炉负荷>一次风率>主燃区空气过量系数>假想切圆直径>燃烧器竖直摆角。

改变导叶翼型对水泵水轮机“S”特性的影响

针对水泵水轮机“S”特性区域的不稳定性问题,提出使用改型活动导叶翼型进行性能提升.以某水泵水轮机模型为研究对象,采用SST k-ω湍流模型对水泵水轮机全流道进行三维数值计算,通过对活动导叶翼型的改型设计,得出流量-转速模拟曲线,分析水泵水轮机组“S”特性改善情况.将计算与试验结果进行对比,并对改型活动导叶翼型前后机组的无叶区进行压力脉动分析.结果表明:在保证整体效率依然保持在92%附近的前提下,新的活动导叶翼型对机组的“S”特性依旧具有改善效果;无叶区压力脉动主要是受到活动导叶叶栅区域的分流在此重新聚集影响,并且与转轮叶片的动静相互扰动引起的;改型后的活动导叶降低了无叶区的压力脉动幅值,提升了水泵水轮机运行中的并网稳定性.

S型异质结光催化剂ZnFe_(2)O_(4)/WO_(3)的构筑及光催化还原CO_(2)性能

通过在WO_(3)纳米片表面负载ZnFe_(2)O_(4)纳米颗粒,构建了一系列S型异质结光催化剂ZnFe_(2)O_(4)/WO_(3),并研究了其光催化CO_(2)还原性能。在没有助催化剂和牺牲剂的条件下,所制备的ZnFe_(2)O_(4)/WO_(3)复合材料可对CO_(2)与水蒸汽进行光催化反应。优化后的材料光照5 h后CO_(2)还原产物CO和CH_(4)的产量分别为7.87和4.88μmol·g^(-1)。相对于单相组分,CO和CH_(4)的产量明显提高。光催化活性的提高,归因于ZnFe_(2)O_(4)和WO_(3)异质结的形成以及光生载流子的S型电荷传输模式。

基于STM32的步进电机加减速轨迹规划算法

针对传统步进电机开环控制下加减速过程中柔性冲击大、失步和过冲等问题,结合STM32单片机提出了一种离散化的、带有电流调节的S曲线加减速控制算法。首先,通过多项式算法构建连续光滑的S曲线,根据矩频特性拟合转速和转矩的关系,联立转速和功率的关系,推导出电流计算方法;然后,对连续的S曲线进行等时间间隔采样,完成对S曲线的离散化;最后,在Keil平台进行算法代码编写,将编译后的工程文件下载到STM32中,通过步进电机的速度和位置跟踪实验验证了算法的有效性。

一种基于随机求反的S盒抗DPA攻击安全结构

DPA攻击(差分功耗攻击)作为一种重要的侧信道攻击方法,因其成功率较高而成为加密算法面临的主要威胁之一。S盒是分组加密算法(高级加密标准(AES)、国产商业密码(SM4)等)中唯一的非线性运算,很大程度上决定了相关加密算法的安全性。S盒的实现主要分为:查表法、组合逻辑和复合域方法。复合域方法因将S盒中的GF(28)域上的求逆运算分解到低阶域上而使其硬件实现具有高性能、低面积等优势。该文提出了一种基于随机求反的复合域S盒抗DPA攻击安全结构,并据此设计了两类抗DPA攻击的AES安全结构:一种是基于随机取反的AES安全结构(RC-AES安全结构),另一种是基于随机取反与一阶掩码结合的AES安全结构(RC-M-AES安全结构)。实验证明,相较于已知文献中基于掩码保护的AES,该文提出的RC-AES结构只需增加微小的面积开销就能有效抵抗DPA攻击,展现出显著的面积优势。同时,RC-M-AES安全结构能在微小面积开销下,构建出比单独掩码方案更安全的密码芯片结构。此外,提出的S盒安全结构不仅适用于AES,也适用于任何以替换函数作为唯一非线性运算的加密算法,具有较好的通用性。

2022年四川芦山M_(S)6.1地震前应力状态研究

为研究2022年6月1日四川芦山M_(S)6.1地震的孕育和发生过程,采用CAP方法反演了2013年芦山M_(S)7.0主震及M_(S)≥5.0余震的震源机制解,并基于应力张量方差与b值时空分布特征,探讨了芦山M_(S)6.1地震的力学机制和震源区的应力状态。结果表明:2022年芦山M_(S)6.1地震震源机制表现出与2013年芦山M_(S)7.0主震和5级余震相似的逆冲型破裂特征,压应力轴方位与龙门山断裂带南段区域应力场一致。2013年芦山M_(S)7.0地震后震中及附近的应力张量方差和b值长期处于低值状态,2022年芦山M_(S)6.1地震前震中及附近出现了应力张量方差和b值的低值异常,表明芦山余震区处于较高的应力水平。分析认为:巴颜喀拉块体持续东向运动受到华南块体的阻挡,震中所在区域长期受挤压逆冲作用,从而使芦山余震区长期处于应力积累的状态,芦山M_(S)6.1地震也是在这种动力学背景下发生的。

基于5S理念的高校实验课程思政教学探索

以提升高校实验课程思政教学水平与育人能力为目标,结合5S现场管理理念,提出高校实验课程思政教学实施方案。阐述了实验现场环境5S管理理念素养训练的可行性,给出实验授课氛围5Y管理素养训练的具体要求,两者结合建立5S5Y管理素养训练理念模型。为了使模型能够长期有效实施,提出将5S与5Y的具体内容、要求置入设计相应管理系统开发思路。结合实际实验课程教学过程,对系统相关具体功能模块进行了设计。该系统能够实现在对高校实验教学过程精细化管理的同时,承载了素养训练的思想,为实验课程思政教学开展提供理念与规范化管理方法借鉴。

阴道卷曲乳杆菌S层蛋白多样性研究

目的:分析比较西安市女性阴道卷曲乳杆菌S层蛋白的多样性及NCBI数据库中阴道来源卷曲乳杆菌S层蛋白的多样性。方法:选取100例妇科患者的阴道分泌物标本作为研究对象,从其中10例标本中分离得到480株卷曲乳杆菌,其中两株卷曲乳杆菌S层蛋白有明显差异,对其进行全基因组测序;并从NCBI数据库中下载人阴道源的卷曲乳杆菌全基因组数据,分析并比较西安市来源与数据库来源的卷曲乳杆菌S层蛋白的多样性。结果:S层蛋白注释基因具有菌株内和菌株间的多样性,同一套基因组中有多个S层蛋白注释基因,菌株间的相似性偏差较大,通过系统发育分析发现,中国人阴道卷曲乳杆菌的S层蛋白基因与其他人种的具有系统发育相似性。结论:阴道卷曲乳杆菌S层蛋白具有菌种间和菌株间多样性的特征,不同人种的卷曲乳杆菌具有相似性。

结合主动光源和改进YOLOv5s模型的夜间柑橘检测方法

【目的】解决夜间环境下遮挡和较小柑橘难以准确识别的问题,实现采摘机器人全天候智能化作业。【方法】提出一种结合主动光源的夜间柑橘识别方法。首先,通过分析主动光源下颜色特征不同的夜间柑橘图像,选择最佳的光源色并进行图像采集。然后,提出一种夜间柑橘检测模型BI-YOLOv5s,该模型采用双向特征金字塔网络(Bi-FPN)进行多尺度交叉连接和加权特征融合,提高对遮挡和较小果实的识别能力;引入Coordinate attention(CA)注意力机制模块,进一步加强对目标位置信息的提取;采用融入Transformer结构的C3TR模块,在减少计算量的同时更好地提取全局信息。【结果】本文提出的BI-YOLOv5s模型在测试集上的精准率、召回率、平均准确率分别为93.4%、92.2%和97.1%,相比YOLOv5s模型分别提升了3.2、1.5和2.3个百分点。在所采用的光源色环境下,模型对夜间柑橘识别的正确率为95.3%,相比白光环境下提高了10.4个百分点。【结论】本文提出的方法对夜间环境下遮挡和小目标柑橘的识别具有较高的准确性,可为夜间果蔬智能化采摘的视觉精准识别提供技术支持。

献血者HBVs基因变异的生物信息学分析

目的分析HBV DNA+/HBsAg-献血者的传染性指标、S区基因序列突变情况及生物信息学特征变化。方法通过PCR方法筛查出1份HBV DNA+/HBsAg-的标本,应用酶联免疫和化学发光方法检测该标本乙肝病毒5项指标,对该标本HBVs区基因片段测序并分析变异情况,应用分析软件对所测序列进行生物信息学分析。结果该标本HBV DNA+、HBsAg-、HBsAb+、HBeAg+、HBeAb-、HBcAb+;HBVs区基因序列内发生氨基酸单位点突变(P151L),空间结构发生改变。结论HBVs区基因序列空间结构改变,可能是导致检测结果出现血清学HBsAg-/HBsAb+/HBV DNA+的原因。

基于C/S架构和物联网技术的可移动医疗设备共享调配系统的设计与应用

目的 设计一个可移动医疗设备高效管理与临床科室共享调配相结合的医疗设备共享管理平台,实现可移动医疗设备使用的全过程管理。方法 基于C/S架构,利用物联网技术优化整合现有医疗设备大数据资源,结合医院需求,构建可移动医疗设备共享调配系统,实现医疗设备共享管理、预约借用、统计分析等核心功能。通过比较系统上线前后呼吸机调配次数、平均调配时间、呼吸机使用率、单台呼吸机日均收入4个指标,分析系统应用效果。结果 系统上线后,呼吸机调配次数明显增加、平均调配时间明显降低,呼吸机使用率、单台呼吸机日均收入明显升高,且差异均有统计学意义(P﹤0.05),表明系统对提高呼吸机调配效率与使用效率有促进作用。结论 可移动医疗设备共享调配系统优化了医院设备管理流程,实现了医疗资源的统一调配,有效满足临床紧急抢救时医疗设备调配使用的相关需求,提高了医疗设备周转率以及设备管理人员的工作效率,有助于医院节约人员成本、降低采购费用,为医院管理者制定相关决策提供数据支撑。

基于改进YOLOv5s的不同成熟度苹果目标检测方法

[目的]本文旨在解决在自然环境下不同成熟度苹果目标检测精度较低的问题。[方法]提出了一种改进的YOLOv5s模型SODSTR-YOLOv5s(YOLOv5s with small detection layer and omni-dimensional dynamic convolution and swin transformer block),用于不同成熟度苹果检测。首先改进YOLOv5s的多尺度目标检测层,在Prediction中构建检测160×160特征图的检测头,提高小尺寸的不同成熟度苹果的检测精度;其次在Backbone结构中融合Swin Transformer Block,加强同级成熟度的苹果纹理特征融合,弱化纹理特征分布差异带来的消极影响,提高模型泛化能力;最后将Neck结构的Conv模块替换为动态卷积模块ODConv,细化局部特征映射,实现局部苹果细粒度特征的充分提取。基于不同成熟度苹果数据集进行试验,验证改进模型的性能。[结果]改进模型SODSTR-YOLOv5s检测的精确率、召回率、平均精度均值分别为89.1%、95.5%、93.6%,高、中、低成熟度苹果平均精度均值分别为94.1%、93.1%、93.7%,平均检测时间为16 ms,参数量为7.34 M。相比于YOLOv5s模型,改进模型SODSTR-YOLOv5s精确率、召回率、平均精度均值分别提高了3.8%、5.0%、2.9%,参数量和平均检测时间分别增加了0.32 M和5 ms。[结论]改进模型SODSTR-YOLOv5s提升了在自然环境下对不同成熟度苹果的检测能力,能较好地满足实际采摘苹果的检测要求。