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Ultrasensitive and accurate diagnosis of urothelial cancer by plasmonic AuNRs-enhanced fluorescence of near-infrared Ag_(2)S quantum dots

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Rare Metals 2022年第11期41卷 3828-3838页

作者： Dong Zhang Cai-Ping Ding Xiao-Yue Zheng Jia-Zhou Ye Zi-Hai Chen Jian-Hua Li Ze-jun Yan jun-Hui Jiang you-ju huang Department of Urology&Nephrology Ningbo First HospitalThe Affiliated Hospital of Zhejiang UniversityNingbo315000China College of Material Chemistry and Chemical EngineeringKey Laboratory of Organosilicon Chemistry and Material TechnologyMinistry of EducationHangzhou Normal UniversityHangzhou311121China Anhui Shenghaitang Traditional Chinese Medicine Decoction Pieces Co. LtdBozhou236800China Anhui Topway Testing Services Co. Ltd.Xuancheng Economic and Technological Development ZoneXuancheng242000China

Urothelial carcinoma(UC)is a common malignant tumor in the urinary system with high recurrence rate and low survival rate 5 years after surgery.At present,imaging examination and other diagnostic methods have some shortcomings such as invasiveness and non-specificity.Therefore,it is urgent to develop a simple,rapid,noninvasive,highly sensitive and highly specific strategy to diagnose UC.Herein,a high-performance fluorescence sensor was constructed by the plasmonic gold nanorods(AuNRs)-enhanced near-infrared(NIR)fluorescence of silver sulfide quantum dots(Ag_(2)S QDs).The designed sensor can be used for the fast and accurate detection of small molecule single-transmembrane protein(FXYD3),which is overexpressed in 90%of ureteral cancers and 84%of high-grade bladder cancers.Due to its high specificity,the NIR fluorescence sensor achieves the detection of FXYD3 in the range of 0.25-150 ng·ml^(-1)with a detection limit of 0.2 ng·ml^(-1).Importantly,it also can be used for accurate diagnosis of FXYD3 in the urine of patients with relevant cancers,and the results are consistent with clinical cystoscopy and pathological analysis.The proposed fluorescence sensor provides a simple,ultrasensitive,reliable method for UC screening,tumor-grade classification and postoperative monitoring and will have great potential for clinical applications.

关键词： Urothelial carcinoma FXYD3 Plasmonic enhanced fluorescence Ultrasensitive Accurate diagnosis

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Multiple regulatory roles of the transfer RNA-derived small RNAs in cancers

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Genes & Diseases 2024年第2期11卷 597-613页

作者： Yu Zhang Xinliang Gu Yang Li Yuejiao huang Shaoqing ju Medical School of Nantong University Nantong UniversityNantongJiangsu 226001China Department of Laboratory Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China Department of Medical Oncology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China

With the development of sequencing technology,transfer RNA(tRNA)-derived small RNAs(tsRNAs)have received extensive attention as a new type of small noncoding RNAs.Based on the differences in the cleavage sites of nucleases on tRNAs,tsRNAs can be divided into two categories,tRNA halves(tiRNAs)and tRNA-derived fragments(tRFs),each with specific subcellular localizations.Additionally,the biogenesis of tsRNAs is tissue-specific and can be regulated by tRNA modifications.In this review,we first elaborated on the classification and biogenesis of tsRNAs.After summarizing the latest mechanisms of tsRNAs,including transcriptional gene silencing,post-transcriptional gene silencing,nascent RNA silencing,translation regulation,rRNA regulation,and reverse transcription regulation,we explored the representative biological functions of tsRNAs in tumors.Furthermore,this review summarized the clinical value of tsRNAs in cancers,thus providing theoretical support for their potential as novel biomarkers and therapeutic targets.

关键词： Biogenesis Biological function Cancer Mechanism Therapeutic strategy tsRNAs

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Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 438-450页

作者： Yu ZHANG Xinliang GU Yang LI Xun LI Yuejiao huang Shaoqing ju Medical School of Nantong University Nantong UniversityNantong 226001China Department of Laboratory Medicine Affiliated Hospital of Nantong UniversityNantong 226001China Research Center of Clinical Medicine Afiliated Hospital of Nantong UniversityNantong 226001China Department of Medical Oncology Afiliated Hospital of Nantong UniversityNantong 226001China

Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.

关键词： Transfer RNA(tRNA)-derived small RNA(tsRNA) Gastric cancer(GC) Acyl-coenzyme A dehydrogenase short/branched chain(ACADSB) Molecular mechanism Treatment Ferroptosis

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Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading:A multicenter retrospective study

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Chinese Medical Journal 2024年第6期137卷 720-728页

作者： ju huang Huimin Liu Dekun Yang Tianming Xu Jing Wang Jingnan Li Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China Key Laboratory of Gut Microbiota Translational Medicine Research Chinese Academy of Medical SciencesBeijing 100730China Department of Gastroenterology Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical CollegeYantaiShandong 264000China Department of Gastroenterology Beijing Zhong-Neng-Jian HospitalBeijing 102401China

Background:The incidence of well-differentiated gastric neuroendocrine tumors(G-NET)is increasing annually,and while they have a good prognosis and low mortality rate,their high recurrence rate makes treatment options controversial.This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.Methods:We performed a multicenter,retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital,Yantai Yuhuangding Hospital,and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023.Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.Results:After a median follow-up of 49 months,the overall recurrence rate among the 94 G-NET patients was 14%(13/94).The recurrence rates of endoscopic mucosal resection(EMR),endoscopic submucosal dissection(ESD),somatostatin analog(SSA)therapy,and surgery were 43%(6/14),10%(5/49),5%(1/22),and 11%(1/9),respectively.Post-treatment recurrence rates were significantly different(P=0.014)among four treatments(EMR,ESD,SSA,and surgery),and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group.From the second month onward,SSA therapy considerably reduced the gastrin levels from 1081.0(571.5,2472.8)pg/mL to 461.5(255.3,795.0)pg/mL(Z=-3.521,P<0.001).Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied,only the pre-treatment gastrin level(P=0.018 and 0.005)and the type of treatment(P=0.014 and 0.017)were significantly associated with G-NET recurrence.Conclusions:Individualized treatment strategies may reduce the risk of relapse after G-NET treatment.Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions,and it substantially decreases the incidence of post-treatment recurrence.

关键词： Well-differentiated G-NET Serum gastrin Personalized treatment Endoscopic submucosal dissection Endoscopic mucosal resection Somatostatin analog therapy Surgical resection Recurrence

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Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

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Nano-Micro Letters 2024年第9期16卷 478-499页

作者： Yao Xiao Zaijin Tao Yufeng ju Xiaolu huang Xinshu Zhang Xiaonan Liu Pavel A.Volotovski Chao huang Hongqi Chen Yaozhong Zhang Shen Liu Department of Orthopaedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital600 Yishan RdShanghai 200233People’s Republic of China Shanghai Tongji Hospital 389 Xincun RdShanghai 200065People’s Republic of China Key Laboratory for Thin Film and Microfabrication of Ministry of Education Research Institute of Micro/Nano Science and TechnologyShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Orthopedic Trauma Department Belarus Republic Scientific and Practical Center for Traumatology and OrthopedicsKizhevatova str.60/4220024 MinskBelarus Shanghai Haohai Biological Technology Limited Liability Company 1386 Hongqiao RdShanghai 200336People’s Republic of China Department of General Surgery Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital600 Yishan RdShanghai 200233People’s Republic of China Shanghai Key Laboratory for High Temperature Materials and Precision Forming School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China

Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.

关键词： Diamond-like carbon Reactive oxygen species scavenging Foreign body reaction Biodegradation Antioxidant Peritendinous adhesion

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dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing

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Regenerative Biomaterials 2024年第2期3卷 100-113页

作者： ju Zhang Ruijuan Si Yu Gao Hui Shan Qi Su Zujian Feng Pingsheng huang Deling Kong Weiwei Wang Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China School of Nursing Qingdao UniversityNingde RoadShinan DistrictQingdaoShandong266071China Cancer Hospital of Tianjin Medical University North Huanhu West RoadTianjinChina The Affliated Hospital of Qingdao University 16 Jjiangsu RoadShinan DistrictQingdaoChina 5NankaiUniver aniin300071.China

Due to its highly insidious and rapid progression,deep tissue pressure injury(DTPI)is a clinical challenge.Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accu-mulation.Decellularized extracellular matrix(dECM)hydrogel promotes skeletal muscle injury repair.However,its role in po-larizing macrophages and regulating iron metabolism in DTPI remains unclear.Here,porcine dECM hydrogel was prepared,and its therapeutic function and mechanism in repairing DTPI were investigated.The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD2o6+macrophages and notably decreased intracellular divalent iron levels.In mice DTPI model,dECM hydrogel treatment promoted M1 to M2 macrophage conversion,improved iron metabolism and reduced oxidative stress in the early stage of DTPI.In the remodeling phase,the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair.Furthermore,the immunomodulation of dEcM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway,as revealed by GO and KEGG pathway analysis,which may ameliorate the iron deposition and promote the healing of DTPI.Our findings indicate that dECM hydrogel is promising in skeletal muscle repair,inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

关键词： Deep tissue pressure injury hydrogel immunomodulation tissue repair

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Integrated neural tracing and in-situ barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors

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Science China(Life Sciences) 2024年第3期67卷 518-528页

作者： Meimei Liao Xinwei Gao Chen Chen Qi Li Qingchun Guo He huang Erquan Zhang Dapeng ju College of Biological Sciences China Agriculture UniversityBeijing 100193China National Institute of Biological Sciences(NIBS) Beijing 102206China Chinese Institute for Brain Research Beijing 102206China School of Biomedical Engineering Capital Medical UniversityBeijing 100069China Department of Anesthesiology The Second Affiliated HospitalChongqing Medical UniversityChongqing 401336China Tsinghua Institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijing 102206China

The circadian clock coordinates rhythms in numerous physiological processes to maintain organismal homeostasis. Since the suprachiasmatic nucleus(SCN) is widely accepted as the circadian pacemaker, it is critical to understand the neural mechanisms by which rhythmic information is transferred from the SCN to peripheral clocks. Here, we present the first comprehensive map of SCN efferent connections and suggest a molecular logic underlying these projections. The SCN projects broadly to most major regions of the brain, rather than solely to the hypothalamus and thalamus. The efferent projections from different subtypes of SCN neurons vary in distance and intensity, and blocking synaptic transmission of these circuits affects circadian rhythms in locomotion and feeding to different extents. We also developed a barcoding system to integrate retrograde tracing with in-situ sequencing, allowing us to link circuit anatomy and spatial patterns of gene expression. Analyses using this system revealed that brain regions functioning downstream of the SCN receive input from multiple neuropeptidergic cell types within the SCN, and that individual SCN neurons generally project to a single downstream brain region.This map of SCN efferent connections provides a critical foundation for future investigations into the neural circuits underlying SCNmediated rhythms in physiology. Further, our new barcoded tracing method provides a tool for revealing the molecular logic of neuronal circuits within heterogeneous brain regions.

关键词： circadian rhythms SCN output circuit neural tracing barcoded GFP in situ sequencing

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Impact of volcanism on the formation and hydrocarbon generation of organic-rich shale in the Jiyang Depression, Bohai Bay Basin, China

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Petroleum Science 2024年第3期21卷 1539-1551页

作者： Jia-Hong Gao Xin-Ping Liang Zhi-jun Jin Quan-you Liu Chang-Rong Li Xiao-Wei huang ju-Ye Shi Peng Li State Key Laboratory of Shale Oil and Gas Enrichment Mechanisms and Efficient Development Institute of Energy Peking University Petroleum Exploration and Production Research Institute SINOPEC School of Energy Resources China University of Geosciences

Globally, most organic-rich shales are deposited with volcanic ash layers. Volcanic ash, a source for many sedimentary basins, can affect the sedimentary water environment, alter the primary productivity, and preserve the organic matter（OM） through physical, chemical, and biological reactions. With an increasing number of breakthroughs in shale oil exploration in the Bohai Bay Basin in recent years, less attention has been paid to the crucial role of volcanic impact especially its influence on the OM enrichment and hydrocarbon formation. Here, we studied the petrology, mineralogy, and geochemical characteristics of the organic-rich shale in the upper submember of the fourth member（Es4～1） and the lower submember of the third member（Es3～3） of the Shahejie Formation, aiming to better understand the volcanic impact on organic-rich shale formation. Our results show that total organic carbon is higher in the upper shale intervals rich in volcanic ash with enriched light rare earth elements and moderate Eu anomalies. This indicates that volcanism promoted OM formation before or after the eruption. The positive correlation between Eu/Eu* and Post-Archean Australian Shale indicates hydrothermal activity before the volcanic eruption. The plane graph of the hydrocarbon-generating intensity（S1+S2） suggests that the heat released by volcanism promoted hydrocarbon generation. Meanwhile, the nutrients carried by volcanic ash promoted biological blooms during Es4～1 and Es3～3 deposition, yielding a high primary productivity. Biological blooms consume large amounts of oxygen and form anoxic environments conducive to the burial and preservation of OM. Therefore, this study helps to further understand the organic-inorganic interactions caused by typical geological events and provides a guide for the next step of shale oil exploration and development in other lacustrine basins in China.

关键词： Volcanic ash Hydrocarbon generation Organic-rich shale Shahejie Formation Jiyang Depression

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Ten- year follow- up investigation of stroke risk in systemic lupus erythematosus

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Stroke & Vascular Neurology 2024年第1期9卷 1-7页

作者： Jin-An huang Ching-Heng Lin Ming-ju Wu Yi-Hsing Chen Kuo-Cheng Chang Chung-Wei Hou Division of Neurology Neurological InstituteTaichung Veterans General HospitalTaichungTaiwan Department of Health Business Administration Hungkuang UniversityTaichungTaiwan Department of Medical Research Taichung Veterans General HospitalTaichungTaiwan Division of Nephrology Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine Chung Shan Medical UniversityTaichungTaiwan College of Medicine National Chung Hsing UniversityTaichungTaiwan Division of Allergy Immunology and RheumatologyDepartment of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine National Yang-Ming Chiao Tung UniversityTaichungTaiwan

Background and purpose To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus(SLE).Methods A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research Database.Patients with SLE between 2000 and 2008 were registered and matched with two controls by the index date,age,gender and Charlson Comorbidity Index(CCI).These subjects were followed until either stroke event or 31 December 2013.Adjusted HRs(aHRs)for strokes were estimated with Cox regression models,and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival analysis.Results In total,8310 patients with SLE and 16620 patients without SLE were included.In general,patients with SLE had higher rates of ischaemic stroke(5.4%vs 3.3%)and haemorrhagic stroke(1.5%vs 0.6%)than in controls.In multivariate analysis adjusted to age,gender,CCI,urbanisation level and antithrombotics uses,aHRs of all strokes,ischaemic stroke and haemorrhagic stroke were 1.73(95%CI:1.54 to 1.94),1.65(95%CI:1.45 to 1.87)and 2.24(95%CI:1.71 to 2.95),respectively,in patients with SLE.Patients with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE,even 10 years after SLE diagnosis(6.12%vs 3.50%,p<0.001).Antiplatelet use increased the risk of haemorrhagic stroke in SLE group(aHR=1.74,95%CI:1.18 to 2.57).Conclusions Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 years.Antiplatelets should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

关键词： erythematosus diagnosis likely

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纳米生物传感器探针材料:合成、组装及应用

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高分子学报 2023年第6期54卷 870-891页

作者：宋丽平朱欣怡黄又举杭州师范大学材料与化学化工学院杭州311121

生物传感器因选择性高、分析速度快、准确度高等特点,在生物医学、环境监测及食品安全等领域应用广泛.纳米探针材料是生物传感器中的核心部件,对检测信号的输出和放大,起到至关重要的作用.本文总结了近十年来本团队利用智能高分子精准... 详细信息

生物传感器因选择性高、分析速度快、准确度高等特点,在生物医学、环境监测及食品安全等领域应用广泛.纳米探针材料是生物传感器中的核心部件,对检测信号的输出和放大,起到至关重要的作用.本文总结了近十年来本团队利用智能高分子精准调控纳米粒子合成的研究成果,发展了多种生长模式,量身定制出三十多种高效可医用探针材料;通过智能高分子修饰纳米探针表面,实现了不同维度(1D、2D和3D)的宏观可控自组装.最后,基于设计的探针材料及其组装结构,构建了一系列生物传感器,探索了其在食品安全检测和医疗诊断领域的应用.

关键词：生物传感器纳米探针智能高分子精准合成可控自组装

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