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Cellular & Molecular Immunology 2024年第3期21卷 245-259页

作者： Yan xin Sihan Xiong linghong Zhou xin lin Institute for Immunology and School of Medicine Tsinghua University100084BeijingChina Tsinghua University-Peking University Center for Life Sciences 100084BeijingChina Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalFudan UniversityShanghai200040China

Invasive fungal infections are life-threatening,and neutrophils are vital cells of the innate immune system that defend against them.The role of LTA4H-LTB_(4)-BLT1 axis in regulation of neutrophil responses to fungal infection remains poorly understood.Here,we demonstrated that the LTA4H-LTB_(4)-BLT1 axis protects the host against Candida albicans and Aspergillus fumigatus,but not Cryptococcus neoformans infection,by regulating the antifungal activity of neutrophils.Our results show that deleting Lta4h or Blt1 substantially impairs the fungal-specific phagocytic capacity of neutrophils.Moreover,defective activation of the spleen tyrosine kinase(Syk)and extracellular signal-related kinase(ERK1/2)pathways in neutrophils accompanies this impairment.Mechanistically,BLT1 regulates CR3-mediated,β-1,3-glucan-induced neutrophil phagocytosis,while a physical interaction with CR3 with slight influence on its dynamics is observed.Our findings thus demonstrate that the LTA4H-LTB_(4)-BLT1 axis is essential for the phagocytic function of neutrophils in host antifungal immune response against Candida albicans and Aspergillus fumigatus.

关键词： LTA4H BLT1 Phagocytosis Complement receptor 3 Fungi

Grain refinement of 5A06 aluminum alloy welds caused by tungsten inert gas welding arc characteristics under Ar-He alternating gas supply conditions:a coupled method of water-cooled copper plate test/numerical simulation

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Journal of Iron and Steel Research(International) 2024年第3期31卷 767-777页

作者： Hong-bin Dai Jian Miao Jia-xin lin School of Materials Science and Engineering Harbin University of Science and TechnologyHarbin 150040HeilongjiangChina

The welding arc,as a carrier for the conversion of electrical energy to thermal energy,has a direct impact on the quality of welding by its properties and states.In the tungsten inert gas(TIG)welding process under the condition of Ar-He alternating gas supply,the arc is alternately converted between Ar arc and He arc with an alternating gas supply cycle,which has obvious arc change characteristics.The FLUENT software was used to numerically simulate the characteristics of the TIG arc under the condition of alternating gas supply,and the arc temperature field,arc pressure,electric potential and current density distribution under the condition of alternating gas supply were obtained.Combined with the real-time data of arc pressure measured by the water-cooled copper plate with holes,it is proved that the TIG arc has obvious dynamic characteristics under the condition of Ar-He alternating gas supply.This unique dynamic TIG arc acts on the 5A06 aluminum alloy weld,causing the molten pool to stir,resulting in uniform microstructure and grain refinement at the weld,and thereby improving the mechanical properties of the welded joint.

关键词： Alternating gas supply Grain refinement Numerical simulation Tungsten argon arc morphology Microstructure Mechanical property

Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 143-151页

作者： HUANG Yong-quan LIU Jia-lin CHEN Geng-xin SHEN Dan-ting ZHU Wang CHEN xin-lin LIU Feng-bin HOU Qiu-ke Graduate School Guangzhou University of Chinese MedicineGuangzhou(510405)China Department of Orthopedics the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Preventive Medicine and Health Statistics Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510405)China

Objective:To evaluate if berberine can act on vitamin D receptors(VDR)and thereby regulate the expression of tight junction proteins(TJPs)in irritable bowel syndrome-diarrhea-predominant(IBS-D)rats.Methods:The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation.After modeling,the model was evaluated and rats were divided into the control group and berberine treatment groups(0.85,1.7 and 3.4 mg/kg,once a day for 2 weeks).The distal colon was obtained and colonic epithelial cells(CECs)were isolated and cultured after IBS-D model evaluation.The vitamin D receptor response element(VDRE)reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter.VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair,and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs.Results:The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner(P<0.05).The activity of VDRE promoter was also effectively promoted by berberine(P<0.05).Berberine increased the expression of TJPs in IBS-D CECs(P<0.05).VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups(all P<0.05).RT-qPCR and Western blot results showed that compared with the blank group,expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups(all P<0.05).Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1(P<0.05).Conclusion:Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity,and the main site of action is the N-terminal region of VDR.

关键词： berberine Chinese medicine irritable bowel syndrome-diarrhea-predominant vitamin D receptors intestinal mucosal barrier tight junction proteins

Effect of hot isostatic pressure on the microstructure and tensile properties of γ'-strengthened superalloy fabricated through induction-assisted directed energy deposition

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International Journal of Minerals,Metallurgy and Materials 2024年第5期31卷 1089-1097页

作者： Jianjun Xu Hanlin Ding xin lin Feng Liu Analytical&Testing Center Northwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China

The microstructure characteristics and strengthening mechanism of Inconel738LC(IN-738LC) alloy prepared by using induction-assisted directed energy deposition(IDED) were elucidated through the investigation of samples subjected to IDED under 1050℃ preheating with and without hot isostatic pressing(HIP,1190℃,105 MPa,and 3 h).Results show that the as-deposited sample mainly consisted of epitaxial columnar crystals and inhomogeneously distributed γ’ phases in interdendritic and dendritic core regions.After HIP,grain morphology changed negligibly,whereas the size of the γ’ phase became increasingly even.After further heat treatment(HT,1070℃,2 h + 845℃,24 h),the γ’ phase in the as-deposited and HIPed samples presented a bimodal size distribution,whereas that in the as-deposited sample showed a size that remained uneven.The comparison of tensile properties revealed that the tensile strength and uniform elongation of the HIP + HTed sample increased by 5% and 46%,respectively,due to the synergistic deformation of bimodal γ’phases,especially large cubic γ’ phases.Finally,the relationship between phase transformations and plastic deformations in the IDEDed sample was discussed on the basis of generalized stability theory in terms of the trade-off between thermodynamics and kinetics.

关键词： directed energy deposition Ni-based superalloys high-temperature preheating hot isostatic pressing microstructure tensile properties

DMF-scMT-seq linking methylome and transcriptome within single cells with digital microfluidics

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Science China Chemistry 2024年第6期67卷 2070-2078页

作者： xing Xu Xi Zeng xin lin Shiyan lin Shanshan Liang Tian Tian Rui Su Jia Song Chaoyong Yang Collaborative Innovation Center of Chemistry for Energy Materials The MOE Key Laboratory of Spectrochemical Analysis and InstrumentationState Key Laboratory of Physical Chemistry of Solid SurfacesDepartment of Chemical BiologyCollege of Chemistry and Chemical EngineeringThe First Affiliated Hospital of Xiamen UniversityXiamen UniversityXiamen361005China Institute of Molecular Medicine Renji HospitalShanghai Jiao Tong University School of MedicineShanghai200127China Chemistry and Materials Science College Shanghai Normal UniversityShanghai200234China Chemistry and Biomedicine Innovation Center(ChemBIC) School of Chemistry and Chemical EngineeringNanjing UniversityNanjing210023China

Single-cell joint analysis of methylome and transcriptome reveals how the methylation regulates the transcriptional activity.However,traditional bench-top protocols for single-cell DNA methylation and RNA transcription co-detection are laborintensive,cost-ineffective and contaminant-prone.Herein,we establish the DMF-sc MT-seq,a highly-efficient and cost-effective method to simultaneously analyze single-cell DNA methylation and transcriptional activity based on digital microfluidics.DMFsc MT-seq automates the workflow of single-cell isolation,cellular hypotonic lysis,nucleic acid separation and methylome/transcriptome library construction in a contactless and addressable way.The system ensures high accuracy(R>0.85),high gene detection ability(14,697 genes per cell at 4 million sequencing depth),and high CpG coverage(677,198 CpG sites per cell at 1million sequencing depth).By using DMF-sc MT-seq,the relationship of DNA methylation and RNA transcription under different genomic contexts is resolved.We further apply DMF-sc MT-seq to study the dynamics of transcription regulation with methylation-inhibiting anti-tumor Decitabine,and identify the methylated promoter/gene body driven genes in response to Decitabine treatment.DMF-sc MT-seq facilitates the construction of the correlation of DNA methylation and transcriptional activity at the single-cell level in a flexible,sensitive and accurate way,which is anticipated to be a powerful tool in studying single-cell biological systems.

关键词： single-cell analysis digital microfluidics methylome sequencing transcriptome sequencing

Optimization of tracheoesophageal fistula model established with Tshaped magnet system based on magnetic compression technique

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World Journal of Gastroenterology 2024年第16期30卷 2272-2280页

作者： Miao-Miao Zhang Jian-Qi Mao lin-xin Shen Ai-Hua Shi xin Lyu Jia Ma Yi Lyu Xiao-Peng Yan Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Shaanxi Provincial Key Laboratory of Magnetic Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Zonglian College Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Pulmonary and Critical Care Medicine The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Department of Surgical Oncology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control.We designed a Tshaped magnet system to overcome these problems and verified its effectiveness via animal experiments.AIM To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs.METHODS Twelve beagles were randomly assigned to groups in which magnets of the Tshaped scheme(study group,n=6)or normal magnets(control group,n=6)were implanted into the trachea and esophagus separately under gastroscopy.Operation time,operation success rate,and accidental injury were recorded.After operation,the presence and timing of cough and the time of magnet shedding were observed.Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing,and gross specimens of TEFs were obtained.Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery,and gross specimens were obtained.Fistula size was measured in all animals,and then harvested fistula specimens were examined by hematoxylin and eosin(HE)and Masson trichrome staining.RESULTS The operation success rate was 100%for both groups.Operation time did not differ between the study group(5.25 min±1.29 min)and the control group(4.75 min±1.70 min;P=0.331).No bleeding,perforation,or unplanned magnet attraction occurred in any animal during the operation.In the early postoperative period,all dogs ate freely and were generally in good condition.Dogs in the control group had severe cough after drinking water at 6-9 d after surgery.X-ray indicated that the magnets had entered the stomach,and gastroscopy showed TEF formation.Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm±1.29 mm(range,3.52-6.56 mm).HE and Masson trichrome staining showed scar tissue formation and hierarchical structural

关键词： Magnetic surgery Magnetic compression technique Tracheoesophageal fistula Magnet Animal model Beagles

Ethanol extract of Abelmoschus manihot suppresses endoplasmic reticulum stress in contrast-induced nephropathy

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 17-27,I0002,I0003页

作者： xin lin xin Lu Yun-He Zhao Yi-Bei Wang Ru-Ge Niu Xiao-Hu Chen Department of Cardiology Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjingJiangsu 210004China

Objective:To explore the efficacy and potential mechanisms of the ethanol extract of Abelmoschus manihot(L.)Medic in contrast-induced nephropathy(CIN).Methods:CIN rat models and human renal proximal tubular cells(HK-2)with iopromide-induced injury were employed to mimic CIN conditions.The effect of Abelmoschus manihot extract on the rat models and HK-2 cells was evaluated.In rat models,kidney function,histology,oxidative stress and apoptosis were determined.In HK-2 cells,cell viability,apoptosis,mitochondrial membrane potential,and endoplasmic reticulum stress were assessed.Results:Abelmoschus manihot extract significantly improved structural and functional impairments in the kidneys of CIN rats.Additionally,the extract effectively mitigated the decline in cellular viability and reduced iopromide-induced oxidative stress and lipid peroxidation.Mechanistic investigations revealed that Abelmoschus manihot extract prominently attenuated acute endoplasmic reticulum stress-mediated apoptosis by downregulating GRP78 and CHOP protein levels.Conclusions:Abelmoschus manihot extract can be used as a promising therapeutic and preventive agent in the treatment of CIN.

关键词： Contrast-induced nephropathy Abelmoschus manihot extract ER stress Apoptosis GRP78 CHOP

Toward understanding the microstructure characteristics,phase selection and magnetic properties of laser additive manufactured Nd-Fe-B permanent magnets

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International Journal of Extreme Manufacturing 2024年第1期6卷 277-294页

作者： Bo Yao Nan Kang Xiangyu Li Dou Li Mohamed EL Mansori Jing Chen Haiou Yang Hua Tan xin lin State Key Laboratory of Solidiffcation Processing Northwestern Polytechnical UniversityXi’anShaanxi 710072People’s Republic of China Arts et Metiers Institute of Technology MSMPHESAM UniversitéF-51006 Chˆalons-en-ChampagneFrance Key Laboratory of Metal High Performance Additive Manufacturing and Innovative Design MIIT ChinaNorthwestern Polytechnical UniversityXi’anShaanxi 710072People’s Republic of China Texas A&M Engineering Experiment Station Institute for Manufacturing SystemsCollege StationTX 77843United States of America

Nd-Fe-B permanent magnets play a crucial role in energy conversion and electronic devices.The essential magnetic properties of Nd-Fe-B magnets,particularly coercivity and remanent magnetization,are significantly infuenced by the phase characteristics and microstructure.In this work,Nd-Fe-B magnets were manufactured using vacuum induction melting(VIM),laser directed energy deposition(LDED)and laser powder bed fusion(LPBF)technologies.Themicrostructure evolution and phase selection of Nd-Fe-B magnets were then clarified in detail.The results indicated that the solidification velocity(V)and cooling rate(R)are key factors in the phase selection.In terms of the VIM-casting Nd-Fe-B magnet,a large volume fraction of theα-Fe soft magnetic phase(39.7 vol.%)and Nd2Fe17Bxmetastable phase(34.7 vol.%)areformed due to the low R(2.3×10-1?C s-1),whereas only a minor fraction of the Nd2Fe14B hard magnetic phase(5.15 vol.%)is presented.For the LDED-processed Nd-Fe-B deposit,although the Nd2Fe14B hard magnetic phase also had a low value(3.4 vol.%)as the values of V(10-2m s-1)and R(1.45×106?C s-1)in the LPBF process resulted in the substantial formation of the Nd2Fe14B hard magnetic phase(55.8 vol.%)directly from the liquid,while theα-Fe soft magnetic phase and Nd2Fe17Bxmetastable phase precipitation are suppressed in the LPBF-processed Nd-Fe-B magnet.Additionally,crystallographic texture analysis reveals that the LPBF-processedNd-Fe-B magnets exhibit isotropic magnetic characteristics.Consequently,the LPBF-processed Nd-Fe-B deposit,exhibiting a coercivity of 656 k A m-1,remanence of 0.79 T and maximum energy product of 71.5 k J m-3,achieved an acceptable magnetic performance,comparable to other additive manufacturing

关键词： laser additive manufacturing(LAM) Nd-Fe-B permanent magnets numerical simulation microstructure magnetic properties

Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment

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Cellular & Molecular Immunology 2024年第1期21卷 47-59页

作者： Yu Zheng Haihui Jiang Naixue Yang Shaoping Shen Daosheng Huang Lemei Jia Jing ling Longchen Xu Mingxiao Li Kefu Yu Xiaohui Ren Yong Cui Xun Lan Song lin xin lin Institute for Immunology and School of Medicine Tsinghua UniversityBeijing100084China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityChina.National Clinical Research Center for Neurological DiseasesCenter of Brain TumorBeijing Institute for Brain Disorders and Beijing Key Laboratory of Brain TumorBeijing100070China Department of Neurosurgery Peking University Third HospitalPeking UniversityBeijing100191China Tsinghua-Peking Center for Life Sciences Beijing100084China

A highly immunosuppressive tumor microenvironment(TME)and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma(HGG).Here,we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C)to establish a robust antitumor immune response in this registered clinical trial(NCT03392545).During the follow-up,12/27(44.4%)patients who achieved tumor control concomitant with survival benefit were regarded as responders in our study.We found that the T-cell receptor(TCR)repertoire in the TME was reshaped after poly(I:C)treatment.Based on the RNA-seq analysis of tumor samples,the expression of annexin A1(ANXA1)was significantly upregulated in the tumor cells of nonresponders,which was further validated at the protein level.In vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1(FPR1)to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C).The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven TME.Moreover,ANXA1 could serve as a reliable predictor of response to poly(I:C),with a notable predictive accuracy rate of 92.3%.In light of these notable findings,this study unveils a new perspective of immunotherapy for gliomas.

关键词： glioma ANXA1 TLR3 poly(I:C) immunotherapy

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis

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Cancer Pathogenesis and Therapy 2024年第2期2卷 91-102页

作者： Lijuan Guo Xiaoyi lin xin lin Yulei Wang Jiali lin Yi Zhang Xiangqing Chen Miao Chen Guochun Zhang Yifang Zhang Department of Breast Surgery Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510000China Schol of Medicine South China University of TechnologyGuangzhouGuangdong 510000China Medical College Shantou UniversityShantouGuangdong 515000China The Second School of Clinical Medicine Southerm Medical UniversityGuangzhouGuangdong 510000China Department of Breast Cancer Guangdong Provincial People's Hospital's Nanhai HospitalFoshanGuangdong 528000China Department of Emergency Medicine Guangdong Provincial People's Hospitals Nanhai HospitalFoshanGuangdong 528000China

Background:Programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)inhibitors have become integral elements within the current landscape of breast cancer treatment modalities;however,they are associ-ated with interstitial lung disease(ILD),which is rare but potentially fatal.Notably,only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors.Therefore,this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors.We also reported three cases of ILD after PD-1 inhibitor treatment.Methods:We comprehensively searched PubMed,EMBASE,and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer.Pooled overall estimates of incidence and risk ratio(RR)were calculated with a 95%confidence interval(CI),and a mirror group analysis was per-formed using eligible studies.Results:This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment.A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors(0.05 vs.0.02).The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors(RR=2.34,95%CI,1.13-4.82,P=0.02).Conclusion:Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors.These findings are instrumental for clinicians in treatment deliberations,and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

关键词： Programmed cell death 1 inhibitor Programmed cell death ligand 1 inhibitor Interstitial lung disease Breast cancer Immune-related adverse events