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IDH1 mutation inhibits differentiation of astrocytes and glioma cells with low oxoglutarate dehydrogenase expression by disturbingα-ketoglutarate-related metabolism and epigenetic modification

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Life Metabolism 2024年第2期3卷 24-37页

作者： Yuanlin Zhao Ying Yang Risheng Yang Chao Sun Xing Gao Xiwen Gu Yuan Yuan Yating Nie Shenhui Xu Ruili Han Lijun Zhang jing Li Peizhen Hu Yingmei Wang Huangtao Chen Xiangmei Cao jing Wu zhe Wang Yu Gu jing Ye State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of PathologyXijing Hospital and School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi 710032China Department of Pathology Air Force Hospital of Southern Theater CommandGuangzhouGuangdong 510000China Department of Neurology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China Department of Clinical Diagnosis Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China Department of Neurosurgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China Department of Pathology School of Basic Medical SciencesNingxia Medical UniversityYinchuanNingxia 750004China Institute of Analytical Chemistry and Instrument for Life Science The Key Laboratory of Biomedical Information Engineering of Ministry of EducationSchool of Life Science and TechnologyXi’an Jiaotong UniversityXi’anShaanxi 710049China

Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary *** IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic ***,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains *** this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as *** low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte ***,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in *** metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in ***,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing ***,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma ***,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.

关键词： α-ketoglutarate IDH1 mutation OGDH l-glutamine gliomas

CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

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International Journal of Oral Science 2024年第1期16卷 134-144页

作者： Xuan Zhou Xinjia Cai Fengyang jing Xuefen Li Jianyun Zhang heyu Zhang Tiejun Li Department of Oral Pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force ***, its role in the regulation of osteoclast differentiation remains unclear. herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

关键词： CD97 osteoclast inhibited

Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang zhe Ma Haiyan Lu hebei Key Laboratory of Stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in ***, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

miR-135a-5p靶向抑制Kif3B调控小鼠腭胚突间充质细胞的自噬

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中国组织工程研究 2024年第19期28卷 3003-3011页

作者：冯文宣廉舒博王哲陈靖何苇遵义医科大学口腔医学院贵州省遵义市563000 遵义医科大学附属口腔医院贵州省遵义市563000

背景:研究表明,在地塞米松诱导腭裂的小鼠胚胎腭突间充质细胞中miR-135a-5p呈高表达,初级纤毛及其介导的Shh信号通路参与小鼠胚胎腭突间充质细胞的自噬。由此猜测miR-135a-5p可能通过初级纤毛及其介导的Shh信号途径调控小鼠胚胎腭突间... 详细信息

背景:研究表明,在地塞米松诱导腭裂的小鼠胚胎腭突间充质细胞中miR-135a-5p呈高表达,初级纤毛及其介导的Shh信号通路参与小鼠胚胎腭突间充质细胞的自噬。由此猜测miR-135a-5p可能通过初级纤毛及其介导的Shh信号途径调控小鼠胚胎腭突间充质细胞的自噬。目的:探讨miR-135a-5p对小鼠胚胎腭突间充质细胞自噬的调控作用。方法:体外提取并培养C57BL/6J小鼠胚胎腭突间充质细胞。细胞转染分别设置为:①对照组、miR-135a-5p阴性对照组、miR-135a-5p模拟物组。②NC+miR-NC组、KIF3B过表达组、miR-135a-5p+KIF3B组。qRT-PCR验证miR-135a-5p、KIF3B的转染效率;透射电镜观察各组细胞中自噬小体/自噬溶酶体的数目;免疫荧光技术测定自噬标记物LC3B的荧光表达程度;Western blot检测KIF3B、LC3和P62的蛋白表达。③miR-135a-5p阴性对照组、SAG处理组、SAG+miR-135a-5p组。qRT-PCR检测Shh信号下游关键转录因子Gli3的mRNA表达水平;Western blot检测自噬相关蛋白LC3和P62的蛋白表达。结果与结论:①过表达miR-135a-5p后,细胞内自噬小体/自噬溶酶体数量显著增多(P<0.01);LC3B的荧光密度显著升高(P<0.01),KIF3B、P62的蛋白表达降低(P<0.01),LC3的蛋白表达升高;②过表达KIF3B后,细胞内自噬小体/自噬溶酶体数目明显减少(P<0.01),LC3B的荧光密度降低(P<0.01),P62的蛋白表达升高(P<0.01),LC3的蛋白表达下降(P<0.01);miR-135a-5p靶向抑制KIF3B的表达(P<0.01),并使自噬小体/自噬溶酶体数目、LC3B的荧光强度以及LC3的蛋白表达得到回升(P<0.01),P62的蛋白表达下降(P<0.01);③SAG使Gli3的mRNA表达明显升高(P<0.01),P62的蛋白表达升高(P<0.01),LC3的蛋白表达下降(P<0.01);加入miR-135a-5p后,Gli3的mRNA表达显著下降(P<0.01),P62的蛋白表达下降(P<0.01),LC3的蛋白表达回升(P<0.01);④结果表明:miR-135a-5p靶向抑制KIF3B并且可能通过负向调控Shh信号通路促进小鼠胚胎间充质细胞自噬。

关键词：自噬胚胎腭突间充质细胞 miRNA KIF3B Shh信号通路腭裂

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工艺误差对AWG串扰特性的影响

通信学报 2003年第8期24卷 65-71页

作者：戴道锌徐静刘书哲何赛灵何建军浙江大学现代光学仪器国家重点实验室光及电磁波研究中心浙江杭州310027

分析了阵列波导光栅器件的制作过程中引入的各种工艺误差。对波导尺寸误差、折射率误差以及长度误差进行了等效,并计算了位相误差和振幅误差的方差。最后分析了位相误差和振幅误差对阵列波导光栅的频谱特性尤其是相邻通道间的串扰特... 详细信息

分析了阵列波导光栅器件的制作过程中引入的各种工艺误差。对波导尺寸误差、折射率误差以及长度误差进行了等效,并计算了位相误差和振幅误差的方差。最后分析了位相误差和振幅误差对阵列波导光栅的频谱特性尤其是相邻通道间的串扰特性的影响。

关键词：工艺误差位相误差振幅误差串扰阵列波导光栅

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基于正交拉丁方的局部修复码构造

浙江大学学报（工学版） 2024年第3期58卷 501-509页

作者：刘帅帅王静刘哲徐忠环长安大学信息工程学院陕西西安710064

针对目前具有(r,t)局部性的局部修复码码率较低且构造过程中计算复杂度过高的问题,提出基于正交拉丁方的二元局部修复码构造方法.根据正交拉丁方元素与矩阵位置的对应关系构造关联矩阵,得到具有全符号局部性的局部修复码(AS-LRCs),该码... 详细信息

针对目前具有(r,t)局部性的局部修复码码率较低且构造过程中计算复杂度过高的问题,提出基于正交拉丁方的二元局部修复码构造方法.根据正交拉丁方元素与矩阵位置的对应关系构造关联矩阵,得到具有全符号局部性的局部修复码(AS-LRCs),该码的码率和码长渐近边界条件,且最小距离较大.利用关联矩阵级联单位矩阵构造信息位具有(r,t=2)局部性的单校验局部修复码,该码的最小距离和码率均满足最优边界条件,为最优局部修复码.考虑到实际分布式存储系统中存在高故障率节点,利用正交拉丁方完备组构造具有信息位局部性的高可用性单校验局部修复码(IS-LRCs),可以灵活选择可用性t,提高了系统的鲁棒性与灵活性.

关键词：分布式存储系统局部修复码正交拉丁方最小距离节点故障率

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast

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World Journal of Clinical Cases 2024年第23期12卷 5320-5328页

作者： Lei zheng Li-Xian Yang jing-Yi Liu zhe Jiang Xiao-Wei Li Peng-Peng Pu Department of Breast Surgery Xingtai People's HospitalXingtai 054001Hebei ProvinceChina Department of Medical Imaging Xingtai People´s HospitalXingtai 054001Hebei ProvinceChina

BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and *** radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for *** To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June *** to the Miller-Payne grading system,the pathological response,***,of the NAC in the initial breast lesion after NAC was *** these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate *** In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(Phe area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,***,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictiv

关键词： Breast cancer Ultrasound Neoadjuvant chemotherapy Efficacy Pathological complete response

Influence of confined water on the limit support pressure of tunnel face in weakly water-rich strata

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Journal of Central South University 2024年第8期31卷 2844-2859页

作者： LI Yun-fa WU Guo-jun CheN Wei-zhong YUAN jing-qiang HUO Meng-zhe State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China

In the process of shield tunneling through soft soil layers,the presence of confined water ahead poses a significant threat to the stability of the tunnel ***,it is crucial to consider the impact of confined water on the limit support pressure of the tunnel *** study employed the finite element method(FEM)to analyze the limit support pressure of shield tunnel face instability within a pressurized water-containing ***,a multiple linear regression approach was applied to derive a concise solution formula for the limit support pressure,incorporating various influencing *** analysis yields the following conclusions:1)The influence of confined water on the instability mode of the tunnel face in soft soil layers makes the displacement response of the strata not significant when the face is unstable;2)The limit support pressure increases approximately linearly with the pressure head,shield tunnel diameter,and tunnel burial *** inversely proportional to the thickness of the impermeable layer,soil cohesion and internal friction angle;3)Through an engineering case study analysis,the results align well with those obtained from traditional theoretical methods,thereby validating the rationality of the equations proposed in this ***,the proposed equations overcome the limitation of traditional theoretical approaches considering the influence of changes in impermeable layer *** can accurately depict the dynamic variation in the required limit support pressure to maintain the stability of the tunnel face during shield tunneling,thus better reflecting engineering reality.

关键词： weakly water-rich strata confined aquifer limit support pressure finite element method multiple linear regression

Correction:Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest

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World Journal of Cardiology 2024年第4期16卷 215-216页

作者： jing-jing Wang Qiang Zhou zhen-Hua Huang Yong Han Chong-zhen Qin Zhong-Qing Chen Xiao-Yong Xiao zhe Deng Department of Emergency Medicine Shenzhen Second People’s Hospital/The First Affiliated Hospital of Shenzhen University Health Science CenterShenzhen 518035Guangdong ProvinceChina Shenzhen Emergency Medical Center Shenzhen 518043Guangdong ProvinceChina

This is an erratum to an already published paper named“Establishment of a prediction model for prehospital return of spontaneous circulation in out-ofhospital patients with cardiac arrest”.We found errors in the aff... 详细信息

关键词： Cardiac arrest Cardiopulmonary resuscitation Recovery spontaneous circulation Logistic regression analysis Predictive model