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High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi chen Ruoyu Zhong ke Jin Ye He Jianping Xia ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke P.Lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various diseases.However,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities.Here,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets.By adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet.We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid biopsies.Due to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

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Two sandwich-type uranyl-containing polytungstates catalyze aerobic synthesis of benzimidazoles

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Rare Metals 2024年第3期43卷 1316-1322页

作者： Yu-Feng Liu Qi-Long Hu Xue-Jiao chen ke Li Pei Luo Guo-Ping Yang School of Chemistry and Material Science Jiangxi Province Key Laboratory of Synthetic ChemistryJiangxi Key Laboratory for Mass Spectrometry and InstrumentationEast China University of TechnologyNanchang330013China School of Environmental Science and Engineering Southern University of Science and TechnologyShenzhen518055China

Diversified synthetic strategies are extremely important for the structural diversity of uranium-containing polyoxometalates(U-POMs)and their functional expansion.Herein,two sandwich-type U-POMs were reported,which are Na_(5.6)K_(6.4)[(UO_(2))(H_(2)O)(TeW_(9)O_(33))]_(2)·21H_(2)O(UTeW_(9))and Na_(8.9)K_(2.7)H_(1.19)[K_(0.79)(UO_(2))_(2.21)(PW_(9)O_(34))_(2)]·12H_(2)O(UPW_9)using in-situ strategy and lacunary precursor strategy,respectively.UTeW_9 shows a typical keggin-typeopen or half-sandwich configuration.

关键词： configuration expansion sandwich

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Microstructure Recrystallization and Mechanical Properties of a Cold-Rolled TiNbZrTaHf Refractory High-Entropy Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第4期37卷 633-647页

作者： Chuan Rong Jieren Yang Xiaoliang Zhao ke Huang Ying Liu Xiaohong Wang Dongdong Zhu Ruirun chen College of Materials Science and Engineering Sichuan UniversityChengdu610065China key Laboratory of Air-Driven Equipment Technology of Zhejiang Province Quzhou UniversityQuzhou324000China School of Materials Science and Engineering Harbin Institute of TechnologyHarbin150001China

The equiatomic TiNbZrTaHf alloy was successfully rolled at room temperature with the reduction of ~ 85%. The microstructure and tensile properties were investigated after cold working and annealing. It was determined that the recrystallization temperature of the TiNbZrTaHf alloy between 850 and 900 ℃. Complete recrystallization and normal grain growth occurred, the high stability of single phase was maintained after annealing at 1000, 1200, and 1400 ℃. But the precipitated phase appeared after long term annealing, as seen after 500 h at 1000 ℃. After cold working, the tensile strength and the elongation of TiNbZrTaHf were 1137 MPa and 25.1%, respectively. The annealed alloy has a high tensile strength (σ_(b )= 863 MPa) and ductility (ε_(e )= 28.5%). Moreover, the oxidation of TiNbZrTaHf alloy at elevated temperatures has a significant impact on its mechanical properties. The poor oxidation resistance of TiNbZrTaHf can accelerate tensile failure by inducing fractures at grain boundaries.

关键词： Refractory high entropy alloy Cold rolling Recrystallization Oxidation resistance Mechanical properties

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Celastrol regulates the oligomeric state and chaperone activity of 𝛼B-crystallin linked with protein homeostasis in the lens

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Fundamental Research 2024年第2期4卷 394-400页

作者： Huaxia Wang Qing Tian Ying Zhang Yibo Xi Lidan Hu ke Yao Jingyuan Li Xiangjun chen Eye Center of the Second Affiliated Hospital Zhejiang University School of Medicine88 Jiefang RoadHangzhou 310009China Institute of Translational Medicine Zhejiang University School of Medicine268 Kaixuan RoadHangzhou 310020China. State key Laboratory of Membrane Biology School of Life SciencesTsinghua UniversityBeijing 100084China The Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Zhejiang Province key Laboratory of Quantum Technology and Device Department of PhysicsZhejiang UniversityZheda Road 38Hangzhou 310027China

Protein misfolding and aggregation are crucial pathogenic factors for cataracts,which are the leading cause of visual impairment worldwide.α-crystallin,as a small molecular chaperone,is involved in preventing protein misfolding and maintaining lens transparency.The chaperone activity of α-crystallin depends on its oligomeric state.Our previous work identified a natural compound,celastrol,which could regulate the oligomeric state of αB-crystallin.In this work,based on the UNcle and SEC analysis,we found that celastrol induced𝛼αB-crystallin to form large oligomers.Large oligomer formation enhanced the chaperone activity of αB-crystallin and prevented aggregation of the cataract-causing mutant αA3-G91del.The interactions between𝛼αB-crystallin and celastrol were detected by the FRET(Fluorescence Resonance Energy Transfer)technique,and verified by molecular docking.At least 9 binding patterns were recognized,and some binding sites covered the groove structure of αB-crystallin.Interestingly,αB-R120G,a cataract-causing mutation located at the groove structure,and celastrol can decrease the aggregates of αB-R120G.Overall,our results suggested celastrol not only promoted the formation of large αB-crystallin oligomers,which enhanced its chaperone activity,but also bound to the groove structure of its α-crystallin domain to maintain its structural stability.Celastrol might serve as a chemical and pharmacological chaperone for cataract treatment.

关键词： αB-crystallin Celastrol Interactions Oligomeric state Chaperone activity Structural stability

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng chen Liutao chen Yuting Han chengyong chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu cheng Liang Susu Liu ke Deng Liangfu chen Shangwu chen Guohui Wan Xiaojian Wu Yonggui Fu Anlong Xu State key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial key Laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well characterized.Here,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration.We found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and migration.Notably,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)sites.Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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Rh(Ⅱ)-catalyzed intermolecular carboamination of pyridines via double Csp^(2)-H bond activations

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Science China Chemistry 2024年第1期67卷 374-382页

作者： Zhongfeng Luo Jingxing Jiang Lifang Zou Xiaoyu Zhou Junshan Liu Zhuofeng ke Fengjuan chen Huanfeng Jiang Wei Zeng key Laboratory of Functional Molecular Engineering of Guangdong Province School of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou 510641China School of Materials Science and Engineering PCFM LabSun Yat-sen UniversityGuangzhou 510275China Guangdong Provincial key Laboratory of Chinese Medicine Pharmaceutics School of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510515China

We disclose the development of the Rh-catalyzed amine-directed remote 5,6-carboamination protocol of pyridines via dual Csp^(2)-H functionalizations.A variety of readily available 2-aminopyridines and 1,2,3-triazoles are allowed for coupling cyclization to access polyfunctionalized azaindoles.Mechanistic studies including DFT calculations unveil that relay carbenoidelectrophilic addition to pyridines and the sequential pyridyl Csp^(2)-H amination are involved in this transformation.The postsynthetic utility of this methodology is showcased by versatile and site-selective modification of azaindoles.

关键词： Rh-catalysis azaindoles pyridyl Csp^(2)-H bond carboamination coupling-cyclization

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Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 77-82页

作者： Wen-Jian Mao Jing Zhou Guo-Fu Zhang Fa-Xi chen Jing-Zhu Zhang Bai-Qiang Li Lu ke Wei-Qin Li Department of Critical Care Medicine Jinling HospitalNanjing Medical UniversityNanjing 210002China Department of Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China National Institute of Healthcare Data Science Nanjing UniversityNanjing 210010China

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

关键词： Anticoagulation Splanchnic venous thrombosis Acute necrotizing pancreatitis Readmission Long-term outcomes

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Targeted mechanical forces enhance the effects of tumor immunotherapy by regulating immune cells in the tumor microenvironment

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Cancer Biology & Medicine 2023年第1期20卷 44-55页

作者： Pengfei Zhu Hongrui Lu Mingxing Wang ke chen Zheling chen Liu Yang Cancer Center Department of Medical OncologyZhejiang Provincial People's Hospital(Affiliated People's HospitalHangzhoul Medical College)Hangzhou 310014China Graduate School of Clinical Medicine Bengbu Medical CollegeBengbu 233000China Department of Gastroenterology&Pancreatic Surgery Zhejiang Provincial People's HospitalHangzhou 310014China

Mechanical forces in the tumor microenvironment(TME)are associated with tumor growth,proliferation,and drug resistance.Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells,thus promoting tumor progression and metastasis.Mechanical signals are transformed into biochemical signals,which activate tumorigenic signaling pathways through mechanical transduction.Cancer immunotherapy has recently made exciting progress,ushering in a new era of“chemo-free”treatments.However,immunotherapy has not achieved satisfactory results in a variety of tumors,because of the complex tumor microenvironment.Herein,we discuss the effects of mechanical forces on the tumor immune microenvironment and highlight emerging therapeutic strategies for targeting mechanical forces in immunotherapy.

关键词： Mechanical force microenvironment immunotherapy extracellular matrix cancer

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Clinical observation of extraction-site incisional hernia after laparoscopic colorectal surgery

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 710-716页

作者： Bao-Hang Fan ke-Li Zhong Li-Jin Zhu Zhao chen Fang Li Wen-Fei Wu Second Clinical Medical College of Jinan University Jinan UniversityShenzhen 518020Guangdong ProvinceChina Department of Gastrointestinal Surgery Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina Department of Radiation Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina

BACKGROUND Laparoscopic colorectal cancer surgery increases the risk of incisional hernia(IH)at the tumor extraction site.AIM To investigate the incidence of IH at extraction sites following laparoscopic colo-rectal cancer surgery and identify the risk factors for IH incidence.METHODS This study retrospectively analyzed the data of 1614 patients who underwent la-paroscopic radical colorectal cancer surgery with tumor extraction through the abdominal wall at our center between January 2017 and December 2022.Diffe-rences in the incidence of postoperative IH at different extraction sites and the risk factors for IH incidence were investigated.RESULTS Among the 1614 patients who underwent laparoscopic radical colorectal cancer surgery,303(18.8%),923(57.2%),171(10.6%),and 217(13.4%)tumors were ex-tracted through supraumbilical midline,infraumbilical midline,umbilical,and off-midline incisions.Of these,52 patients developed IH in the abdominal wall,with an incidence of 3.2%.The incidence of postoperative IH was significantly higher in the off-midline incision group(8.8%)than in the middle incision groups[the supraumbilical midline(2.6%),infraumbilical midline(2.2%),and umbilical incision(2.9%)groups](χ^(2)=24.985;P<0.05).Univariate analysis showed that IH occurrence was associated with age,obesity,sex,chronic cough,incision infection,and combined diabetes,anemia,and hypopro-teinemia(P<0.05).Similarly,multivariate analysis showed that off-midline incision,age,sex(female),obesity,incision infection,combined chronic cough,and hypoproteinemia were independent risk factors for IH at the site of laparoscopic colorectal cancer surgery(P<0.05).CONCLUSION The incidence of postoperative IH differs between extraction sites for laparoscopic colorectal cancer surgery.The infraumbilical midline incision is associated with a lower hernia rate and is thus a suitable tumor extraction site.

关键词： Incisional hernia Laparoscopy Colorectal cancer Incision infection

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Pancreatic giant malignancy simulating a gastrointestinal stromal tumor

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 431-433页

作者： Ben-Jie Liu chen-Hui Jin Yan-Lun Guo Zhi-Gang ke Jun-Jun Huang Lin-Ping Cao Department of Hepatobiliary Surgery Department of General SurgeryPujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China Department of Pathology Pujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Pancreatic acinar cell carcinoma(PACC)is a rare malignant tumor of pancreatic epithelial cells,which produces pancreatic exocrine enzymes.PACC originates from acinar cells and terminal branches of the pancreatic ducts in the exocrine tissue of the pancreas.PACC accounts for 1%−2%of pancreatic exocrine tumors[1].Herein,we present an elderly woman with PACC who recovered after effective laparoscopic surgery.The tumor was located on the left side of the abdomen;imaging suggested that it was a gastrointestinal stromal tumor of the gastric wall origin,infiltrating the tail of the pancreas and omentum,while postoperative pathology suggested PACC.

关键词： Pancreatic gastrointestinal pancreas

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