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Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1412-1427页

作者： Jianpei xu Yinzhe Sun Yang You Yuwen Zhang Dan Huang Songlei Zhou Yipu Liu Shiqiang Tong Fenfen Ma Qingxiang Song Chengxiang Dai Suke Li Jigang Lei Zhihua Wang Xiaoling Gao Jun Chen Shanghai Pudong Hospital&Department of Pharmaceutics School of PharmacyFudan UniversityShanghai 201203China Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China Department of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related GenesShanghai Universities Collaborative Innovation Center for Translational MedicineShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Emergency Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Institute of Science and Technology for Brain-Inspired Intelligence&Department of Neurology Fudan UniversityShanghai 201203China Department of Rehabilitation Medicine Huashan HospitalFudan UniversityShanghai 201203China Daxing Research Institute University of Science and Technology BeijingBiomedical Industry BaseZhongguancun Science and Technology ParkBeijing 102600China Cellular Biomedicine Group Inc. Shanghai 201210China

Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical *** levels of deadly reactive oxygen radicals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs’*** on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC *** system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective *** this system,extracellular ROSscavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a microlivable niche at the level of a single MSC for ***,the infarct’s inanimate milieu is transformed at the tissue level into a new living niche to facilitate *** engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 *** vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

关键词： Ischemic stroke Mesenchymal stem cell Cell engineering Hormesis effect Bioorthogonal chemistry Microglia Reactive oxygen spices Proinflammatory cytokines

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Study on Antitumor Activity of Piperidine Derivatives

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Agricultural Biotechnology 2024年第3期13卷 81-85,89页

作者： Zhenwei NIE Hongxia LI Weizhen LI Hangyu MENG Wei xu School of Biological and Food Engineering Suzhou UniversitySuzhou 234000China

[Objectives]This study was conducted to investigate the effects of piperidine derivatives on the proliferation and apoptosis of tumor cells(Hele).[Methods]The target end product(piperidine derivative)was synthesized through a series of organic *** MTT assay was adopted to detect the effect of piperidine derivative on the proliferation activity of Hele *** ROS fluorescence probe method was used to detect the changes of reactive oxygen *** JC-1 method was applied to detect the changes of MMP in Hele *** cytometry was adopted to detect the apoptosis of Hele cells.[Results]The cell survival rates were 70.84%,65.46%and 54.48%when the drug concentration was 100,110 and 120μmol/L,*** the drug concentration increased to 120μmol/L,the cell survival rate decreased by nearly *** fluorescence intensity of active oxygen in the control group was 1,and when the drug concentrations were 100,110 and 120μmol/L,the fluorescence intensity of active oxygen was,respectively,1.315,1.478 and 1.677,which were higher than that in the control *** red/green fluorescence intensity of the MMP control group was 1.819,and that of drug groups was,respectively,1.643,1.164 and 0.665,which were lower than that of the control *** apoptosis rates were 10.79%,22.91%and 38.54%at the drug concentrations of 100,110 and 120μmol/L,respectively,showing a concentration dependent *** results showed that the piperidine derivative could inhibit the proliferation of Hele cells and induce apoptosis,which was positively correlated with the concentration.[Conclusions]This study provides theoretical basis and reference for the anti-tumor research of piperidine.

关键词： Piperidine derivative Hele cell Anti-cancer activity

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矩形顶管隧道F型承插接头剪切刚度分析

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中国铁道科学 2024年第2期45卷 113-122页

作者：许有俊康佳旺张朝庞跃魁黄正东张旭内蒙古科技大学土木工程学院内蒙古包头014010 内蒙古科技大学矿山安全与地下工程院士专家工作站内蒙古包头014010 内蒙古科技大学内蒙古自治区高校城市地下工程研究中心内蒙古包头014010 苏交科集团股份有限公司江苏南京210019

矩形顶管F型承插接头属于柔性接头,地表超载、地基不均匀沉降等极易导致管节间出现剪切错台变形,进而引发隧道工程灾害。基于目前研究中对该种接头剪切力学特性尚不清楚的现状,考虑矩形顶管隧道F型承插接头构造特征,结合室内接头试验和A... 详细信息

矩形顶管F型承插接头属于柔性接头,地表超载、地基不均匀沉降等极易导致管节间出现剪切错台变形,进而引发隧道工程灾害。基于目前研究中对该种接头剪切力学特性尚不清楚的现状,考虑矩形顶管隧道F型承插接头构造特征,结合室内接头试验和ABAQUS三维精细化数值模拟,针对接头在剪切荷载下的破坏过程、刚度特性及影响因素等问题开展研究。结果表明:矩形顶管接头发生剪切破坏时,受载管节呈中心对称破坏;不同地层中接头的剪力-剪切位移曲线均分为建立接触阶段、钢套环翘曲阶段和焊缝开裂3个阶段,地基刚度越大时,其相对剪切刚度越大;钢套环厚度和宽度增加时,刚度系数值随之提高;随着钢套环宽度、厚度增大,接头抗剪能力随之提高,但提高的幅度有限,不同厚度、宽度钢套环的屈服阶段刚度系数约为弹性阶段的60%~70%。

关键词：隧道工程矩形顶管剪切破坏特征剪切刚度数值模拟

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活力激发与秩序重构:党建引领基层群众自治的双重目标

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党政研究 2024年第2期 111-122,M0008页

作者：许宝君四川大学马克思主义学院四川大学成都市新时代基层社会治理现代化研究基地四川成都610200

党建引领基层群众自治是中国式基层治理现代化的重要面向,具有活力激发和秩序重构双重目标。活力是社会发展的动力来源,也是基层群众自治的价值取向。党建引领基层群众自治就是要规范政府行政权力,积累社区社会资本,妥善处理好政府职能... 详细信息

党建引领基层群众自治是中国式基层治理现代化的重要面向,具有活力激发和秩序重构双重目标。活力是社会发展的动力来源,也是基层群众自治的价值取向。党建引领基层群众自治就是要规范政府行政权力,积累社区社会资本,妥善处理好政府职能部门与基层群众自治组织的关系,提升群众参与自治的积极性。秩序是稳定的社会状态,是保障自治活力的基石。党建引领基层群众自治就是要制定自治规则、规避自治冲突、重构自治秩序,使基层群众自治可以健康发展。但双重目标内涵的活力和秩序有内在张力,党组织能够通过纵向空间的规权与赋权、横向空间的组织与动员、网络空间的协商与合作三重机制化解两者张力,解决“既要又要”的问题,保持活力与秩序的动态平衡。

关键词：党建引领党的建设基层群众自治基层治理活力与秩序

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Single-cell landscape of malignant ascites frompatients with metastatic colorectal cancer

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Cancer Communications 2024年第7期44卷 713-717页

作者： Haiyang Zhou Jiahui Yin Anqi Wang Xiaomao Yin Taojun Jin Kai xu Lin Zhu Jiexuan Wang Wenqiang Wang Wei Zhang Xinxiang Li Zhiqian Hu Xinxing Li Division of Colorectal Surgery Changzheng HospitalNavy Medical UniversityShanghaiP.R.China Institute of Higher Education Tongji UniversityShanghaiP.R.China Department of Gastrointestinal Surgery Tongji HospitalTongji University School of MedicineShanghaiP.R.China Department of Gastroenterology Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiP.R.China Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China

The presence of malignant ascites in colorectal cancer(CRC)patients is associated with a poor prognosis,a high risk of recurrence,and resistance to chemotherapy and immune therapy[1–3].Understanding the complex interactions among different kinds of cells and the ecosystem of peritoneal metastasized colorectal cancer(pmCRC)ascites may provide insights into effective treatment strategies.

关键词： ascites colorectal patients

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Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang xueyan Zhou Sitong Qian Jinfang Song Yi xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological ***,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains ***,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH *** the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH *** of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)***’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 *** findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

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Infrared small target detection based on density peaks searching and weighted multi-feature local difference

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Optoelectronics Letters 2024年

作者： JI Bin FAN Pengxiang WANG Mengli LIU Yang xu Jiafeng School of Computer Science and Technology， Anhui University of Technology

In order to solve the problems of unknown target size， fuzzy edges， background interference and low contrast in infrared small target detection， this paper proposes an infrared small target detection method based on density peaks searching and weighted multi-feature local difference. Firstly， for the interference problem of high brightness clutter on the density peaks searching to obtain candidate targets， this paper adopts the improved high-boost filter for preprocessing， which effectively eliminates the background clutter and high brightness background interference in the infrared image， and improves the probability of the true target being captured in the density peaks searching process. Secondly， triple-layer windows are used to extract features from the area around the candidate target， which solves the problem of uncertain size of small targets. Additionally， by calculating the multiple feature local differences between triple-layer windows， the problem of blurred edges and low contrast for the targets are also resolved. In order to balance the contribution degree of different feature local differences to target detection， this paper introduces the intra-class distance to calculate the weight of each feature local differences， realizes the weighted fusion of multi-feature local differences， obtains the weighted multi-feature local difference of each candidate target， and extracts the real target from the candidate target through the interquartile range. Experiments on many different types of infrared image sequences consisting of publicly available datasets such as SIRST and IRSTD-1K show that the method proposed in this paper is applicable to a wide range of complex types with good robustness and detection performance.

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Duchenne型肌营养不良患儿心脏损伤特征随年龄变化趋势的前瞻性队列研究

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中华儿科杂志 2024年第3期62卷 223-230页

作者：胡梅徐婷许可郭应坤余莉许华燕蔡晓唐傅航四川大学华西第二医院放射科出生缺陷与相关妇儿疾病教育部重点实验室成都610041 四川大学华西第二医院病案管理科出生缺陷与相关妇儿疾病教育部重点实验室成都610041 四川大学华西第二医院康复科出生缺陷与相关妇儿疾病教育部重点实验室成都610041

目的探讨Duchenne型肌营养不良(DMD)患儿心脏损伤特征随年龄的变化趋势及其临床意义。方法前瞻性队列研究。纳入215例2019年1月至2022年11月于四川大学华西第二医院确诊为DMD、年龄为6~18岁的患儿为研究对象。收集并分析首诊时的基本临... 详细信息

目的探讨Duchenne型肌营养不良(DMD)患儿心脏损伤特征随年龄的变化趋势及其临床意义。方法前瞻性队列研究。纳入215例2019年1月至2022年11月于四川大学华西第二医院确诊为DMD、年龄为6~18岁的患儿为研究对象。收集并分析首诊时的基本临床资料、心肌标志物、常规心电图、心脏磁共振成像(CMR)、超声心动图等检查指标。将患儿按年龄分为6~<8岁、8~<10岁、10~<12岁、12~<14岁、14~18岁共5组。对照组纳入122名正常男性儿童匹配DMD患儿相应年龄组。分年龄段对DMD患儿与对照组的一般资料和CMR检查指标进行比较,同时比较各年龄段DMD患儿行超声心动图与CMR评估左心室射血分数(LVEF)的差异,组间比较采用独立样本t检验或Mann-Whitney U检验。采用Pearson或Spearman相关分析法分析DMD患儿CMR检查指标与年龄的相关性。结果纳入215例DMD患儿(均为男童)和122名正常男童。6~<8岁DMD患儿75例,对照组23例;8~<10岁DMD患儿77例,对照组28例;10~<12岁DMD患儿39例,对照组23例;12~<14岁DMD患儿10例,对照组31例;14~18岁DMD患儿14例,对照组17例。DMD患儿年龄越大,肌酸激酶、肌酸激酶同工酶(CK-MB)值越低,6~<8岁组肌酸激酶为10760(7800,15757)U/L,14~18岁组为2369(1480,6944)U/L,6~<8岁组CK-MB为(189±17)μg/L,14~18岁组为(62±16)μg/L;肌钙蛋白I在<12岁各组中变化不明显,但在12~<14岁组有较明显升高,达到最高值0.112(0.006,0.085)μg/L。DMD患儿年龄越大,心电图异常比例越高,6~<8岁组为29.3%(22/75),14~18岁组为10/14。DMD患儿左心室舒张末期容积指数与年龄呈正相关(r=0.18,P=0.015),左心室每搏量指数和心输出量指数均与年龄呈负相关(r=-0.34、-0.31,均P<0.001)。DMD患儿年龄越大,LVEF越低,其中14~18岁组的LVEF低至(49.3±3.1)%。8~<10岁、10~<12岁、12~<14岁、14~18岁组的DMD患儿LVEF值均明显低于对照组[(57.9±5.2)%比(63.6±0.8)%、60.7%(55.9%,61.9%)比63.7%(60.2%,66.0%)、57.1%(51.8%,63.4%)比62.1%(59.5%,64.5%)、(49.3±3.1)%比(61.6±1.3)%,均P<0.05]。DMD患儿年龄越大,钆对比剂延迟强化(LGE)发生率越高,6~<8岁组为22%(11/51),12~<14岁组为13/14,14~18岁组均发生LGE。在6~<8岁组与8~<10岁组,超声心动图测出的LVEF均高于CMR测出的LVEF[63.2%(60.1%,66.4%)比59.1%(55.4%,62.9%)、(62.8±5.2)%比(57.9±5.2)%,均P<0.001]。结论DMD患儿在病程早期即存在心脏受累,且随着年龄增加和病程延长,心脏损伤发生率逐渐提高。

关键词：肌营养不良,杜氏心脏损伤心肌疾病

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Cerebral pseudoinfarction due to venoarterial extracorporeal membrane oxygenation:A case report

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World Journal of Clinical Cases 2024年第17期12卷 3130-3137页

作者： Mi xu Jue-Yue Yan Jia-Jia Jin Tong Li Department of Critical Care Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Neurological complications are common in the management of venoarterial extracorporeal membrane oxygenation(VA-ECMO),with most patients requiring sedation and intubation,limiting the assessment of neurological ***,we must rely on advanced neuroimaging techniques,such as computed tomography angiography(CTA)and computed tomography perfusion(CTP).Because ECMO changes the normal blood flow pattern,it may interfere with the contrast medium in some special cases,leading to artifacts and ultimately misleading clinical *** SUMMARY A 61-year-old man presented to a local hospital with chest tightness and pain 1 d prior to *** patient was treated with VA-ECMO after sudden cardiac and respiratory arrest at a local *** further treatment,the patient was transferred to our *** initial consciousness assessment was not clear,and routine CTP was performed to understand the intracranial changes,which suggested a large area of cerebral infarction on the right side;however,the cerebral oxygen was not consistent with the CTP results,and the reexamination of CTA still suggested a right cerebral *** identify this difference,bedside transcranial Doppler was performed,and the blood flow on both sides was *** reducing the ECMO flow,CTP reexamination showed that the results were normal and consistent with the clinical *** day 3,the patient was alert and showed good limb *** In patients with peripheral VA-ECMO,cerebral perfusion confirmed by CTP and CTA may lead to false cerebral infarction.

关键词： Extracorporeal membrane oxygenation Computed tomography perfusion Computed tomography angiography Cerebral perfusion Contrast medium artifacts Case report

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Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang Department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina Department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina Department of General Surgery Tianjin Medical University General HospitalTianjinChina Department of Anorectal Tianjin People's HospitalTianjinChina Department of Radiology Beijing Friendship Hospital Capital Medical UniversityBeijingChina Department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Thoracic Surgery/Institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

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