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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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Construction of a predictive model for gastric cancer neuroaggression and clinical validation analysis: A single-center retrospective study

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2602-2611页

作者： yu-Yin lan Jing Han Yan-Yan Liu Lei lan Department of Stomatology Shanghai Municipal Hospital of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghai 200071China Department of Biobank Zhejiang Cancer HospitalHangzhou 310005Zhejiang ProvinceChina Department of General Surgery Peking University First HospitalBeijing 100034China Department of Oncology Zhejiang HospitalHangzhou 310013Zhejiang ProvinceChina

BACKGROUND This study investigated the construction and clinical validation of a predictive model for neuroaggression in patients with gastric *** cancer is one of the most common malignant tumors in the world,and neuroinvasion is the key factor affecting the prognosis of ***,there is a lack of systematic analysis on the construction and clinical application of its prediction *** study adopted a single-center retrospective study method,collected a large amo-unt of clinical data,and applied statistics and machine learning technology to build and verify an effective prediction model for neuroaggression,with a view to providing scientific basis for clinical treatment decisions and improving the tr-eatment effect and survival rate of patients with gastric *** To investigate the value of a model based on clinical data,spectral computed to-mography(CT)parameters and image omics characteristics for the preoperative prediction of nerve invasion in patients with gastric *** A retrospective analysis was performed on 80 gastric cancer patients who under-went preoperative energy spectrum CT at our hospital between January 2022 and August 2023,these patients were divided into a positive group and a negative group according to their pathological *** data were collected,the energy spectrum parameters of primary gastric cancer lesions were measured,and single factor analysis was performed.A total of 214 image omics features were extracted from two-phase mixed energy images,and the features were screened by single factor analysis and a support vector *** variables with statist-ically significant differences were included in logistic regression analysis to construct a prediction model,and the performance of the model was evaluated using the subject working characteristic *** were statistically significant differences in sex,carbohydrate antigen 199 expression,tumor thickness,Lauren classification

关键词： Gastric neoplasms Nerve invasion Tomography X-ray computer Imaging omics Diagnostic differentiation

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Fc receptor-like 5(FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma

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Signal Transduction and Targeted Therapy 2024年第2期9卷 724-737页

作者： Zhengyu yu Hexian Li Qizhong Lu Zongliang Zhang Aiping Tong Ting niu Department of Hematology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell(CAR-T)*** targets of CAR-T cells used in MM immunotherapy have limitations,with a subset of patients experiencing antigen loss resulting in ***,novel targets for enhancing CAR-T cell therapy in MM remain *** receptor-like 5(FCRL5)is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions,offering an alternative treatment for *** further explore this option,we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models,specifically focusing on MM with gain of chromosome *** the challenges in CAR-T therapies arising from limited T cell persistence,our approach incorporates interleukin-15(IL-15),which enhances the functionality of central memory T(TCM)cells,into the design of FCRL5-directed CAR-T cells,to improve cytotoxicity and reduce T-cell dysfunction,thereby promoting greater CAR-T cell survival and *** in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy,effectively inhibiting the proliferation of MM cells and leading to remarkable tumor *** results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency,suggesting a potential novel immunotherapeutic strategy for MM treatment.

关键词： directed thereby offering

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Multivariate chemical analysis:From sensors to sensor arrays

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Chinese Chemical Letters 2024年第7期35卷 14-24页

作者： Xueling yu Lixing Fu Tong Wang Zhixin Liu Na niu Ligang Chen College of Chemistry Chemical Engineering and Resource UtilizationKey Laboratory of Forest Plant EcologyNortheast Forestry UniversityHarbin 150040China

Chemical sensor arrays can obtain more comprehensive analyte information through high-dimensional *** is of great significance in the analysis of multi-component complex *** review summarizes the development and status of chemical sensor *** focused on the design of chemical sensor arrays based on various sensing *** addition,several pattern recognition methods in chemometrics are *** applications of chemical sensor arrays in food monitoring,medical diagnosis,and environmental monitoring are *** on the analysis of the limitations of current sensor array technology,the direction of the array is also *** review aims to help the broad readership understand the research state of chemical sensor arrays and their development prospects.

关键词： Chemical sensor arrays Sensing materials Pattern recognition methods Analytical application

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Histological,transcriptomic,and gene functional analyses reveal the regulatory events underlying gibberellin-induced parthenocarpy in tomato

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Horticultural Plant Journal 2024年第1期10卷 156-170页

作者： Shaobo niu yu He Siwei Yan Zhengliang Sun Run Cai Yan Zhang Shaanxi Engineering Research Center for Vegetables College of HorticultureNorthwest A&F UniversityYanglingShaanxi 712100China

Gibberellin(GA)is one of the major plant hormones that promote parthenocarpy,a highly valuable agronomic ***,we demonstrated that exogenous GA3application triggered the formation of parthenocarpic fruits with smaller size but unchanged shape in tomato(Solanum lycopersicum).These fruits exhibited a thicker pericarp,undeveloped ovules,and few jelly tissues,leading to smaller locules with empty *** investigation showed that GA treatment produced more cell layers with larger cells in the pericarp,suggesting its promotion in both cell division and *** analyses between GA-3and mock-treated unpollinated ovaries/fruits identified a large number of differentially expressed genes related to hormones,cell division,cell expansion,and transcription factors,implying that they coordinately regulated parthenocarpy conferred by *** particular,the downregulation of five reported repressors of tomato parthenocarpy,including two auxin signaling components,AUXIN RESPONSE FACTOR5(SlARF5)and Sl ARF7,and three MADS-box genes,TOMATO APETALA3(TAP3),TOMATO PISTILLATA(TPI),and AGAMOUS-LIKE6(SlAGL6),after GA treatment might play a key role in this ***,we found that the knockdown of a GA signaling factor SlMYB33,which was depressed by GA treatment,induced parthenocarpic fruit set in tomato,an effect that might have been achieved by enhancing GA biosynthesis and decreasing the expression of some repressors of tomato ***,our results provide a basis for understanding the regulatory mechanism of GA in tomato parthenocarpy.

关键词： Tomato Gibberellin Parthenocarpy Histology Transcriptome SlMYB33

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Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

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Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing lan Zhiqiang Wei Jianqiang yu Jian Zhang School of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

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Molecularly imprinted sensor based on carboxylated carbon nanotubes/Keggin-type polyoxometalates nanocomposite for the detection of furazolidone

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Tungsten 2024年第2期6卷 394-409页

作者： yu-lan Huang Bing Zhang yu-Lian Li Li Wang Le Dong Jian Li College of Ocean Food and Biological Engineering Jimei UniversityXiamen 361021China College of Oceanology and Food Science Quanzhou Normal UniversityQuanzhou 362000China

Due to its properties of mutagenic,teratogenic,and carcinogenic,the detection of furazolidone(FZD)in aquaculture is of great importance for food safety and human *** this study,molecularly imprinted fi lms modifi ed with carboxylated multi-walled carbon nanotube-phosphomolybdic acid composite were used to fabricate an electrochemical sensor for the determination of *** nanocomposites were characterized using infrared spectroscopy,scanning electron microscopy,energy-dispersive X-ray spectroscopy,and X-ray diff *** electrochemical characteristics of the modifi ed electrodes were examined using electrochemical impedance spectroscopy,cyclic voltammetry,and diff erential pulse *** sensor exhibited exceptional catalytic *** calibration curves were acquired in the concentration range of 6 nmol·L^(−1)to 0.6μmol·L^(−1),with a limit of detection of 3.38 nmol·L^(−1).Additionally,the sensor proved successful in recognizing FZD in shrimp samples with satisfactory recoveries and *** method provides a strategy to construct a molecularly imprinted electrochemical sensing platform using nanomaterials,which has great promise in the field of food safety.

关键词： Phosphomolybdate Furazolidone Polyoxometalates Carboxylated multi-walled carbon nanotube Molecularly imprinted polymers Electrochemical sensor

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Holevo bound independent of weight matrices for estimating two parameters of a qubit

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Chinese Physics B 2024年第2期33卷 137-143页

作者：牛畅郁司夏 Department of Modern Physics&Hefei National Research Center for Physical Sciences at the Microscale and School of Physical Sciences University of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China

Holevo bound plays an important role in quantum metrology as it sets the ultimate limit for multi-parameter estimations,which can be asymptotically *** for some trivial cases,the Holevo bound is implicitly defined and formulated with the help of weight *** we report the first instance of an intrinsic Holevo bound,namely,without any reference to weight matrices,in a nontrivial ***,we prove that the Holevo bound for estimating two parameters of a qubit is equivalent to the joint constraint imposed by two quantum Cramér–Rao bounds corresponding to symmetric and right logarithmic *** weightless form of Holevo bound enables us to determine the precise range of independent entries of the mean-square error matrix,i.e.,two variances and one covariance that quantify the precisions of the estimation,as illustrated by different estimation *** result sheds some new light on the relations between the Holevo bound and quantum Cramer–Rao *** generalizations are discussed.

关键词： quantum metrology quantum Fisher information Holevo bound quantum multi-parameter estimation

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A Brief of Cold Spell Warning Actions of the National Meteorological Center of China Meteorological Administration

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China CDC weekly 2024年第5期6卷 88-91页

作者： Taiyuan Zhang Mengxue Zhang Qiutong Li yu lan Huafeng Meteorological Media Group of China Meteorological Administration(CMA) BeijingChina National Institute of Environmental Health Chinese Center for Disease Control and PreventionBeijingChina The National Meteorological Center of China Meteorological Administration(CMA) BeijingChina

The“Outline for High-Quality Development of Meteorology(2022-2035)”was published by the State Council of the People’s Republic of China in April 2022(1).This publication highlights the essential role of meteorological disaster warnings,particularly cold spell warnings,in preventing and mitigating *** outline also sets forth stricter expectations for enhancing the overall capacity of society in terms of meteorological disaster preparedness and response.

关键词： disaster meteorological warning

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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 196–380 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 196–380 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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