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Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

Cancer Biology & Medicine 2024年第1期21卷 45-64页

作者： Jiawen Zhang Sihui Yu Qiao Peng ping Wang lan Fang Tongji University Cancer Center Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Reproductive Medicine Center Department of Obstetrics and GynecologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China Department of Obstetrics and Gynecology Zhongshan HospitalFudan UniversityShanghai 200032China

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer *** this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key *** cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor ***,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer *** strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint *** approaches have shown promise in preclinical and clinical settings,by enhancing patient survival *** review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and ***,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy *** challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.

关键词： cGAS-STING pathway type I interferon cyclic dinucleotide STING agonist cancer immunotherapy

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Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

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BIOCELL 2024年第1期48卷 149-162页

作者： ping YANG YUANXIANG lan ZHONG ZENG YAN WANG HECHUN XIA Department of Neurosurgery School of Clinical MedicineNingxia Medical UniversityYinchuanChina Key Laboratory of Ningxia Stem Cell and Regenerative Medicine General Hospital of Ningxia Medical UniversityYinchuanChina Department of Neurosurgery Xi’an International Medical Center HospitalXi’anChina

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of ***&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in *** primary objective is to provide evidence supporting the clinical application of ***:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after ***,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal *** intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted *** the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3.levels in glutamate-induced HT22 cells compared with conventional ***,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and ***:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

关键词： Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases

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Microdeletion on Xq27.1 in a Chinese VACTERL-Like Family with Kidney and Anal Anomalies

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Biomedical and Environmental Sciences 2024年第5期37卷 503-510页

作者： LI Min ZHANG Yu lan ZHANG Kai Li LI ping ping LYU Yu Han LIANG Ya Xin YU Yue Department of Gynecology and Obstetrics Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing HospitalBeijing 100730China The Key Laboratory of Geriatrics Beijing Institute of GeriatricsBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective VATER/VACTERL-like association is associated with adverse pregnancy *** evidence of this disorder is *** this study,we aimed to provide genetic insights to improve the diagnosis of *** We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like *** and genetic analyses were conducted using genome and exome *** Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–3.0 kb microdeletion on Xq27.1,which was identified by familial exome *** sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 *** family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in *** These results suggest that the 196–3.0 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like ***,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

关键词： Prenatal diagnosis VACTERL whole-genome sequencing whole-exome sequencing X-linked

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Poly(3.hexylthio) thiophene Field-effect Transistor Device Performance: Impact of the Content of Hexylthio Side Chain on Backbone

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Chinese Journal of Polymer Science 2024年第1期42卷 14-23,I0005页

作者： Hao-Yu Liu Lian-He Han Ling-Wei Kong Li-ping Zhu Xiao-lan Qiao Mei-Fang Zhu State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai 201620China School of Electronic Information and Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Regioregular poly(3.hexylthio)thiopene(P3.TT) has emerged tremendous potential in organic electronic applications due to the strong noncovalent interactions from the sulfur atom linked to thiophene. However, P3.TT generally exhibits low charge mobility mostly due to poor solution processability attributed to dense arrangement of hexylthio side chain in polymer, which led to strong noncovalent interactions among sulfur atoms. To balance the nonvalent interaction and aggregation for P3.TT, herein, we systematically study the effect of hexylthio side chain content in polymer backbone on the structure and properties. A series of regioregular P3.TT-based homopolymers(P3.TT, P3.TT-50,P3.TT-3. and P3.TT-25) were prepared via Kumada catalyst transfer polycondensation method from a set of mono-, bi-, ter-and quarterthiophenes containing different contents of hexylthio side chain. The DFT calculation shows the planarity of polymers backbone could be improved through reducing the density of hexylthio side chain in polymer mainchain. And significant changes in their crystallinity, aggregation and optical properties were observed with the content of hexylthio side chain reducing. The P3.TT-3. displayed the highest field-effect transistor hole mobility of 2.83.10^(-2) cm^(2)·V^(-1)·s^(-1) resulting from a balance between the crystallinity and planarity. This study demonstrates modulating the content of hexylthio side chain in P3.TT is an effective strategy to optimize the opto-electronic properties of polymer obtaining excellent semiconductor device performance.

关键词： Conjugated polymer Polythiophene Noncovalent interaction Molecular aggregation Organic field-effect transistor

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Cyclic Pulsating Pressure Enhanced Segregating Structuration of Ultra-High Molecular Weight Polyethylene/Graphene Composites as High-performance Light-Weight EMI Shields

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Chinese Journal of Polymer Science 2024年第7期42卷 958-967,I0008页

作者： Yun-Zhi Huang Xiao-Xiao Liu lan-Wei Li Guang-Ming Huang Zhao-Xia Huang Jin-ping Qu National Engineering Research Center of Novel Equipment for Polymer Processing Key Laboratory of Polymer Processing EngineeringMinistry of EducationGuangdong Provincial Key Laboratory of Technique and Equipment for Macromolecular Advanced ManufacturingSchool of Mechanical and Automotive EngineeringSouth China University of TechnologyGuangzhou 510641China School of Advanced Manufacturing Technology Guangdong Mechanical&Electrical PolytechnicGuangzhou 510550China

Currently,the enhancement in electromagnetic interference(EMI)performance of polymeric composite generally relies on either improving electrical conductivity(σ)for stronger electromagnetic(EM)reflections or tailoring structure for higher EM ***,we proposed a novel technique called cyclic pulsating pressure enhanced segregating structuration(CPP-SS),which can reinforce these two factors *** structural information was supplied by optical microscopy(OM)and scanning electron microscopy(SEM),both of which confirmed the formation and evolution of segregate structured ultra-high molecular weight polyethylene(UHMWPE)/graphene ***,the result showed that CPP-SS can significantly improve theσof ***,advanced specific EMI shielding efficiency of 3..1 d B/mm was achieved for UHMWPE/graphene composite at 1-mm thickness and a low graphene loading of 5 wt%.Meanwhile,it also confirmed that the intrinsic disadvantage of poor mechanical properties of conventional segregated structure composites can be *** work is believed to provide a fundamental understanding of the structural and performance evolutions of segregated structured composites prepared under CPPSS,and to bring us a simple and efficient approach for fabricating high-performance,strong and light-weight polymeric EMI shields.

关键词： Cyclic pulsating pressure Segregated structure Ultra-high molecular weight polyethylene Graphene Electromagnetic interface

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Targeted DNA N^(6)-methyladenine editing by dCas9 fused to METTL4 in the lepidopteran model insect Bombyx mori

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Insect Science 2024年第2期31卷 646-650页

作者： Feng Chen Hao Guo Weiqun lan Mingyi Zhou Wenjng Geng Guanwang Shen ping Lin Qingyou Xia ping Zhao Zhiqing Li Integrative Science Center of Germplasm Creation in Western China(CHONGQING)Science City Biological Science Research CenterSouthwest UniversityChongqingChina Chongqing Key Laboratory of Sericultural Science Chongqing Engineering and Technology Research Center for Novel Silk MaterialsSouthwest UniversityChongqingChina

Dear Editor,N^(6)-Methyladenine(6mA)DNA modification is an important epigenetic mechanism with roles in regulating gene expression,nucleosome positioning,DNA damage repair,and cell cycle progression(Heyn&Esteller,2015;Luo et al.,2015;Boulias&Greer,2022).Despite progress in understanding the biological functions of 6mA,the contribution of individual 6mA installations on site-specific target genes is largely unknown,and therefore deciphering the molecular mechanism of 6mA in target gene expression has been difficult.

关键词： adenine fused Bombyx

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Clinical nursing value of predictive nursing in reducing complications of pregnant women undergoing short-term massive blood transfusion during cesarean section

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World Journal of Clinical Cases 2024年第1期12卷 51-58页

作者： Li Cheng Li-ping Li Yuan-Yuan Zhang Fang Deng Ting-Ting lan Department of Obstertrics Wuhan Third HospitalWuhan 430000Hubei ProvinceChina Department of Gynaecology Wuhan No.1 HospitalWuHan 430030Hubei ProvinceChina Center for Reproductive Medicine Department of Obstetrics and GynecologySichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina

BACKGROUND Cesarean hemorrhage is one of the serious complications,and short-term massive blood transfusion can easily cause postoperative infection and physical stress ***,predictive nursing intervention has important clinical significance for *** To explore the effect of predictive nursing intervention on the stress response and complications of women undergoing short-term mass blood transfusion during cesarean section(CS).METHODS A clinical medical record of 100 pregnant women undergoing rapid mass blood transfusion during sections from June 2019 to June *** to the different nursing methods,patients divided into control group(n=50)and observation group(n=50).Among them,the control group implemented routine nursing,and the observation group implemented predictive nursing intervention based on the control ***,compared the differences in stress res-ponse,complications,and pain scores before and after the nursing of pregnant women undergoing rapid mass blood transfusion during *** The anxiety and depression scores of pregnant women in the two groups were significantly improved after nursing,and the psychological stress response of the observation group was significantly lower than that of the control group(P<0.05).The heart rate and mean arterial pressure(MAP)of the observation group during delivery were lower than those of the control group,and the MAP at the end of delivery was lower than that of the control group(P<0.05).Moreover,different pain scores improved significantly in both groups,with the observation group considerably less than the control group(P<0.05).After nursing,complications such as skin rash,urinary retention,chills,diarrhea,and anaphylactic shock in the observation group were 18%,which significantly higher than in the control group(4%)(P<0.05).CONCLUSION Predictive nursing intervention can effectively relieve the pain,reduce the incidence of complications,improve mood and stress response,and serve as a

关键词： Predictive care Rapid mass blood transfusion Cesarean section Stress response Complications

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Bidirectional effects of the tryptophan metabolite indole-3.acetaldehyde on colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2697-2715页

作者： Ze Dai Kai-Li Deng Xiao-Mei Wang Dong-Xue Yang Chun-lan Tang Yu-ping Zhou Department of Gastroenterology The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Institute of Digestive Disease of Ningbo University Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology Ningbo Key LaboratoryNingbo 315020Zhejiang ProvinceChina

BACKGROUND Colorectal cancer(CRC)has a high incidence and *** studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of *** To investigate the effect of indole-3.acetaldehyde(IAAD)on *** The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity *** apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium *** was investigated using the transwell *** blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream *** PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String *** IAAD reduced tumorigenesis in a syngeneic mouse *** CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the *** results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of *** can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 *** low concentrations(3.aldehyde can induce cell apoptosis and inhibit cell prol

关键词： Indole-3.acetaldehyde Colorectal cancer Tryptophan metabolism Apoptosis Epithelial-mesenchymal transition

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小肽分子对植物养分信号调控和有害元素耐受作用的研究进展

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植物营养与肥料学报 2024年第7期30卷 1367-1376页

作者：兰平中国科学院南京土壤研究所/土壤与农业可持续发展国家重点实验室江苏南京211135 中国科学院大学南京学院江苏南京211135

在自然和农业生态系统中,固着生活的植物时刻面临各种生物和非生物胁迫,其中养分缺乏、养分失衡和重金属毒害极大地限制了植物的生长发育,导致作物产量和品质大幅下降。及时高效感知养分状态并做出适应性改变是植物赖以生存和繁衍生息... 详细信息

在自然和农业生态系统中,固着生活的植物时刻面临各种生物和非生物胁迫,其中养分缺乏、养分失衡和重金属毒害极大地限制了植物的生长发育,导致作物产量和品质大幅下降。及时高效感知养分状态并做出适应性改变是植物赖以生存和繁衍生息的关键。经过长期的自然选择,植物已进化出一整套适应养分匮缺和应对有害元素胁迫的分子机制,包括对养分信号的感知与信号的级联传递,激活基因活性,重塑转录组、蛋白组和代谢组,最后导致生理生化和表型变化。植物感知养分信号分子调控网络一直是植物营养领域的研究热点。小肽通常指小于100个氨基酸长度的功能性肽段,参与植物生长发育的调控、植物和微生物的互作以及生物和非生物逆境的应答。本文就植物内源性小肽分子在养分信号调控、有害元素耐受等方面的最新研究进展进行阶段性总结和讨论,重点围绕小肽在大量元素氮、磷、硫和微量元素铁以及有害元素镉和砷等吸收平衡方面的作用展开,并对未来的研究方向进行展望。

关键词：养分信号小肽氮磷铁硫镉砷

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Development of a diagnostic nomogram for alpha-fetoproteinnegative hepatocellular carcinoma based on serological biomarkers

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2463-2475页

作者： Li He Cui Zhang lan-lan Liu Li-ping Huang Wen-Jing Lu Yuan-Yuan Zhang De-Yong Zou Yu-Fei Wang Qing Zhang Xiao-Li Yang School of Clinical Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of Organ Transplantation The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Department of Laboratory Medicine The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Department of Laboratory Medicine Jingyu County People’s HospitalBaishan 135200Jilin ProvinceChina School of Laboratory Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death *** biomarkers play an important role in the early diagnosis and prognosis of *** a certain percentage of HCC patients are negative for alpha-fetoprotein(AFP),the diagnosis of AFP-negative HCC is essential to improve the detection rate of *** To establish an effective model for diagnosing AFP-negative HCC based on serum tumour *** A total of 180 HCC patients were enrolled in this *** expression levels of GP73.des-γ-carboxyprothrombin(DCP),CK18-M65,and CK18-M3. were detected by a fully automated chemiluminescence *** variables were selected by logistic regression *** models were constructed using stepwise backward logistic *** performance of the models was compared using the C statistic,integrated discrimination improvement,net reclassification improvement,and calibration *** clinical utility of the nomogram was assessed using decision curve analysis(DCA).RESULTS The results showed that the expression levels of GP73.DCP,CK18-M65,and CK18-M3. were significantly greater in AFP-negative HCC patients than in healthy controls(P3.DCP,and CK18-M65 were independent factors for diagnosing AFP-negative *** comparing the diagnostic performance of multiple models,we included GP73.and CK18-M65 as the model variables,and the model had good discrimination ability(area under the curve=0.946)and good goodness of *** DCA curves indicated the good clinical utility of the *** Our study identified GP73.and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative *** diagnostic nomogram based on CK18-M65 combined with GP73.demonstrated good performance and effectively identified high-risk groups of patients with HCC.

关键词： Hepatocellular carcinoma Alpha-fetoprotein-negative Diagnostic Nomogram Biomarker

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