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Antigen presentation,autoantibody production,and therapeutic targets in autoimmune liver disease

Cellular & Molecular Immunology 2021年第1期18卷 92-111页

作者： Andrea Kristina Horst Kingsley Gideon Kumashie Katrin Neumann Linda Diehl Gisa Tiegs institute of Experimental Immunology and Hepatology University Medical Center Hamburg-EppendorfMartinistraBe 52D-20251 HamburgGermany hamburg Center for Translational Immunology University Medical Center Hamburg-EppendorfMartinistraBe 52D-20251 HamburgGermany

The liver is an important immunological organ that controls systemic *** liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and *** the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment,which Is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating *** response to pathogens or autoantigens,tolerance is disrupted by unknown *** parenchymal and nonparenchymal cells exhibit unique antigen-presenting *** presentation of microbial and endogenous lipid-,metabolite-and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or *** of this balance results in autoimmune liver diseases,such as autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing *** the exact etiologies of these autoimmune liver diseases are unknown,it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids,as well as alterations in bile acid composition,may result in changes in effector cell activation and polarization and may reduce or impair protective antiinflammatory regulatory T and B cell ***,the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different(non)immune cells in the liver may play a role in the induction of hepatic inflammation and ***,we summarize emerging aspects of antigen presentation,autoantibody production,and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.

关键词： liver tolerance autoimmune liver disease antigen presentating cell

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22-gauge core vs 22-gauge aspiration needle for endoscopic ultrasound-guided sampling of abdominal masses

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World Journal of Gastroenterology 2016年第39期22卷 8820-8830页

作者： William Sterlacci Athanasios D Sioulas Lothar Veits Pervin G?nüllü Guido Schachschal Stefan Groth Mario Anders Christos K Kontos Theodoros Topalidis Andrea Hinsch Michael Vieth Thomas R?sch Ulrike W Denzer institute of pathology Clinic of Bayreuth Department of Interdisciplinary Endoscopy University Hospital Hamburg-Eppendorf Department of Biochemistry and Molecular Biology University of Athens institute of pathology institute of pathology University Hospital Hamburg-Eppendorf

AIM To compare the aspiration needle(AN) and core biopsy needle(PC) in endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) of abdominal *** Consecutive patients referred for EUS-FNA were included in this prospective single-center trial. Each patient underwent a puncture of the lesion with both standard 22-gauge(G) AN(Echo Tip Ultra; Cook Medical, Bloomington, Indiana, United States) and the novel 22 G PC(Echo Tip Pro Core; Cook Medical, Bloomington, Indiana, United States) in a randomized fashion; histology was attempted in the PC group only. The main study endpoint was the overall diagnostic accuracy, including the contribution of histology to the final diagnosis. Secondary outcome measures included material adequacy, number of needle passes, and *** Fifty six consecutive patients(29 men; mean age 68 years) with pancreatic lesions(n = 38), lymphadenopathy(n = 13), submucosal tumors(n = 4), or others lesions(n = 1) underwent EUS-FNA using both of the needles in a randomized order. AN and PC reached similar overall results for diagnostic accuracy(AN: 88.9 vs PC: 96.1, P = 0.25), specimen adequacy(AN: 96.4% vs PC: 91.1%, P = 0.38), mean number of passes(AN: 1.5 vs PC: 1.7, P = 0.14), mean cellularity score(AN: 1.7 vs PC: 1.1, P = 0.058), and complications(none). A diagnosis on the basis of histology was achieved in the PC group in 36(64.3%) patients, and in 2 of those as the sole modality. In patients with available histology the mean cellularity score was higher for AN(AN: 1.7 vs PC: 1.0, P = 0.034); no other differences were of statistical *** Both needles achieved high overall diagnostic yields and similar performance characteristics for cytological diagnosis; histological analysis was only possible in 2/3 of cases with the new needle.

关键词： Endoscopic ultrasound Cytology Fine needle aspiration Abdominal tumors Core biopsy needle

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涎腺膜性基底细胞腺瘤的临床病理研究

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中华口腔医学杂志 2000年第2期35卷 88-90,I009页

作者：俞光岩 JuergenUssmueller KarlDonath 北京医科大学口腔医学院口腔颌面外科 100081 institute of pathology university of hamburg martinistrabe institute of pathology university of hamburg martinistrabe

目的　探讨涎腺膜性基底细胞腺瘤的临床病理特点及生物学行为。方法　对 1 2例患者进行临床病理分析。结果　肿瘤由大小及形态不一的上皮团块所组成 ,团块外周细胞呈栅栏状排列 ,由玻璃样变的基底膜样物质围绕。 4例伴头皮皮肤圆柱瘤 ,... 详细信息

目的　探讨涎腺膜性基底细胞腺瘤的临床病理特点及生物学行为。方法　对 1 2例患者进行临床病理分析。结果　肿瘤由大小及形态不一的上皮团块所组成 ,团块外周细胞呈栅栏状排列 ,由玻璃样变的基底膜样物质围绕。 4例伴头皮皮肤圆柱瘤 ,8例为多灶性肿瘤 ,1例恶变伴颈淋巴结转移。结论　诊断时应注意与实性型基底细胞腺瘤、基底细胞腺癌、实性型腺样囊性癌以及基底样鳞状细胞癌相鉴别。治疗应作全腮腺切除。

关键词：涎腺肿瘤病理学膜性基底细胞瘤腺瘤

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Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

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World Journal of Gastroenterology 2006年第40期12卷 6515-6521页

作者： Emre F Yekebas Dean Bogoevski Michael Bubenheim Bjrn-Christian Link Jussuf T Kaifi Robin Wachowiak Oliver Mann Asad Kutup Guellue Cataldegirmen Lars Wolfram Andreas Erbersdobler Christoph Klein Klaus Pantel Jakob R Izbicki Department of General Visceral and Thoracic Surgery University Medical Centre of Hamburg-Eppendorf Hamburg Germany institute of Medical Biometry and Epidemiology University Medical Centre of Hamburg-Eppendorf Hamburg Germany institute of pathology University Medical Centre of Hamburg-Eppendorf Hamburg Germany institute of Immunology University of Munich Munich Germany institute of Tumor Biology University Medical Centre of Hamburg-Eppendorf Hamburg Germany

AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pT1/2, 63 （59%） as pT3/4, 51 （48%） as pNo, and 55 （52%） as pN1. The study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULTS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. Twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.

关键词： Pancreatic ductal adenocarcinoma Nodal microinvolvement Micrometastases

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Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

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Cancer Biology & Medicine 2021年第1期18卷 245-255页

作者： Andreas Marx Lena Koopmann Doris Hoflmayer Franziska Büscheck Claudia Hube-Magg Stefan Steurer Till Eichenauer Till S.Clauditz Waldemar Wilczak Ronald Simon Guido Sauter Jakob R.Izbicki Hartwig Huland Hans Heinzer Markus Graefen Alexander Haese Thorsten Schlomm Christian Bernreuther Patrick Lebok Sarah Bonk institute of pathology Klinikum FurthFurth 90766Germany institute of pathology University Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Urology University Medical Center Hamburg-EppendorfHamburg 20246Germany General Visceral and Thoracic Surgery Department and ClinicUniversity Medical Center Hamburg-EppendorfHamburg 20246Germany Martini-Clinic Prostate Cancer CenterUniversity Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Urology Charité-Universit?tsmedizin BerlinBerlin 10117Germany

Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel *** expression is restricted to prostate epithelial *** exact function is *** study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa ***:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer ***7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative *** ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT ***:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in ***7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa.

关键词： ANO7 immunohistochemistry prognosis prostate cancer

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L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma

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World Journal of Gastroenterology 2006年第1期12卷 94-98页

作者： Jussuf T Kaifi Ulrich Zinnkann Emre F Yekebas Paulus G Schurr Uta Reichelt Robin Wachowiak Henning C Fiegel Susann Petri Melitta Schachner Jakob RIzbicki Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburgGermany institute for pathology University Medical Center Hamburg-EppendorfHamburgGermany Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburgGermany Center for Molecular Neurobiology University Medical Center Hamburg-EppendorfHamburgGermany

AIM： To determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. METHODS： We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody U3127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendo- crine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULTS： LI was detected in 5 （7.9%） of 63 pancreatic neuroendocrine tumors. Four （44.4%） of 9 poorlydifferentiated carcinomas expressed L1. In contrast, only 1 （1.9%） of 54 well-differentiated tumors or carcinomas was positive for LI. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas （P〈0.01）. CONCLUSION： L1 is specifically expressed in poorlydifferentiated pancreatic neuroendocrine carcinomas that are known to have the worst prognosis. L1 might be a marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.

关键词： Neuroendocrine pancreatic tumor Tumor markers Cell adhesion molecules L1

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Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers

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Cancer Biology & Medicine 2019年第2期16卷 319-330页

作者： Andreas M. Luebke Ali Attarchi-Tehrani Jan Meiners Claudia Hube-Magg Dagmar S. Lang Martina Kluth Maria Christina Tsourlakis Sarah Minner Ronald Simon Guido Sauter Franziska Buscheck Frank Jacobsen Andrea Hinsch Stefan Steurer Thorsten Schlomm Hartwig Huland Markus Graefen Alexander Haese Hans Heinzer Till S. Clauditz Eike Burandt Waldemar Wilczak Doris Hoflmayer institute of pathology University Medical Center Hamburg-Eppendorf Hamburg 20246 Germany General Visceral and Thoracic Surgery Department and Clinic University Medical Center Hamburg-Eppendorf Hamburg 20246 Germany Department of Urology Charite-Universitatsmedizin Berlin Berlin 10117 Germany Martini-Clinic Prostate Cancer Center University Medical Center Hamburg-Eppendorf Hamburg 20246 Germany

Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is ***: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was ***: PSP94 expression was increased in benign prostatic hyperplasia;however, it was downregulated in 48% and negative in42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression(P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis(P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52%in pT3 b-pT4(P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8(P <0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect(P < 0.0001).However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10%(P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason ***: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.

关键词： MSMB PSP94 PTEN prostate cancer tissue microarray

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CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

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Cellular & Molecular Immunology 2023年第2期20卷 201-213页

作者： Ana Jordan-Paiz Glòria Martrus Fenja L.Steinert Max Kaufmann Adrian F.Sagebiel Renée R.C.E.Schreurs Anne Rechtien Martin E.Baumdick Johannes M.Jung Kimberly J.Möller Lucy Wegner Cordula Grüttner Laura Richert Roland Thünauer Jennifer Schroeder-Schwarz Johannes Bvan Goudoever Teunis B.H.Geijtenbeek Marcus Altfeld Steven T.Pals Daniel Perez Paul L.Klarenbeek Christian Tomuschat Guido Sauter Ingo Königs Udo Schumacher Manuel A.Friese Nathaniel Melling Konrad Reinshagen Madeleine J.Bunders Department of Virus Immunology Leibniz Institute of VirologyHamburg20251Germany university Medical Center hamburg-Eppendorf Hamburg20246Germany institute of Neuroimmunology and Multiple Sclerosis Center for Molecular Neurobiology HamburgUniversity Medical Center Hamburg-EppendorfHamburg20251Germany Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburg20246Germany Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterUniversity of Amsterdam and Vrije Universiteit AmsterdamAmsterdam1105 AZThe Netherlands I.Department of Medicine University Medical Center Hamburg-EppendorfHamburg20246Germany Partner Site hamburg-Lübeck-Borstel-Riems German Center for Infection Research(DZIF)Hamburg20246Germany university of Bordeaux Institut National de la Santéet de la Recherche MédicaleBordeaux Population Health Research Center UMR1219 and INRIA SISTM TeamBordeaux33000France institute of Anatomy and Experimental Morphology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of pathology Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Rheumatology and Clinical Immunology and Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1007 MBThe Netherlands Amsterdam Rheumatology&Immunology Center Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburg20246Germany institute of pathology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pediatric Surgery Altona Children’s HospitalHamburg22763Germany III.Department of Medicine University M

Gastrointestinal infections are a major cause for serious clinical complications in *** induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human *** CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to *** findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to ***-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B *** together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

关键词： TFH cells B cells Antibodies Intestine Pediatrics

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Expression of toxin-related human mono-ADP-ribosyltransferase 3 in human testes

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Asian Journal of Andrology 2006年第3期8卷 281-287,386页

作者： MaikFriedrich AndreasGrahnert Uwe Paasch Andrea Tannapfel Friedrich Koch-Nolte Sunna Hauschildt institute Division of Andrology Department of Dermatology institute of pathology University of LeipzigD-04103 LeipzigGermany institute of Immunology University HospitalD-20246 HamburgGermany

Aim:To investigate wether the corresponding protein of mono-ADP-ribosyltransferase 3(ART3)mRNA is ex- pressed in human testes and,if so,whether the expression is cell ***:ART3 mRNA was deter- mined in human testes and sperm by reverse transcription-polymerase chain reaction(RT-PCR).The glycosyl- phosphatidylinositol linkage of ART3 was shown by treating ART3-transfected HEK-293-T cells with phospholipase *** activated cell sorter(FACS)-analyses were used to detect ART3 on mature spermatozoa and immuno- histological studies to detect the protein in ***:ART3 protein was shown to be present in *** was found on spermatocytes *** was absent from spermatogonia,spermatids and *** absence of ART3 from spermatozoa was confirmed by ***3 protein was detected neither within a seminoma nor on Leydig ***:Here we show for the first time that ART3 protein is expressed in testes in particular on spermatocytes,indicating that ART3 exerts a specific function only required at a particular stage of spermatogenesis.

关键词： mono-ADP-ribosyltransferase 3 testes human spermatocyte spermatogenesis

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Differentiation of Fungal Destructive Behaviour of Wood by the White-Rot Fungus Fomes fomentarius by MALDI-TOF Mass Spectrometry

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Journal of Renewable Materials 2021年第3期9卷 381-397页

作者： Ehsan Bari Antonio Pizzi Olaf Schmidt Siham Amirou Mohammad Ali Tajick-Ghanbary Miha Humar Department of Wood Sciences and Engineering Technical Faculty of No.1Mazandaran BranchTechnical and Vocational University(TVU)SariIran Department of Industrial Chemistry ENSTIB-LERMABUniversity of LorraineEpinalFrance Department of Wood Biology University of HamburgHamburgGermany Department of Mycology and Plant pathology College of Agronomic SciencesAgricultural and Natural Resources UniversitySariIran Department of Wood Science and Technology Biotechnical FacultyUniversity of LjubljanaLjubljanaSlovenia

There are many methods to identify and recognize the molecular and behavioural differences between *** of the methods for the detection and identification of unknown organisms as well as intermolecular and intramolecular structural differences is MALDI-TOF mass ***,differentiation of Fomes fomentarius decay capabilities on the chemical properties of the wood cell wall of the tree species Quercus castaneifolia,Juglans regia,and Carpinus betulus were used to determine and characterize the destructive behaviour of *** decay by MALDI-TOF mass *** results showed that the fungus had more significant destructive behaviour on *** than the other *** this evidence,completely removal of xylan hemicellulose fragment+Na+at peak 1227 Da and severe digestion of fragment of glucomannan hemicellulose at peak 1477–1480 Da that it seems that signs of soft-rot patterns were obtained from the decayed sample of ***,while these were incremental and unchanged for *** and ***,***,*** had different peaks of atomic mass than *** and *** wood,*** results showed that this technique could be useful for separating and identifying unknown compounds of the wood cell wall attacked by fungi relying on their biological behaviour.

关键词： White-rot Fomes fomentarius MALDI-TOF fungal destructive behaviours

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