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Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun Sun Yinglin Xia division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological samples.Metabolomics is emerging as a powerful tool generally for pre-cision medicine.Particularly,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and disease.However,metabo-lomics data are very complicated.Preprocessing/pretreating and normalizing procedures on metabolomics data are usually required before statistical analysis.In this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data transformation.We discuss the advantages and limitations of each method.The choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis method.We then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii infections in critically ill patients:Experience at a tertiary-care teaching hospital ICU

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Journal of Intensive Medicine 2024年第2期4卷 181-186页

作者： Leyla Ferlicolak Neriman Defne Altintas Fugen Yoruk department of Internal Medicine division of Intensive Care Unit Ankara University Faculty of MedicineAnkaraTurkey department of Infectious Diseases and Clinical microbiology Ankara University Faculty of MedicineAnkaraTurkey

Background Acinetobacter baumannii is a clinically significant pathogen with a high incidence of multidrug resistance that is associated with life-threatening nosocomial infections.Here,we aimed to provide an insight into the clinical characteristics and outcomes of a unique group of A.baumannii infections in which the isolates were resistant to carbapenems and most other antibiotic groups in a tertiary-care intensive care unit(ICU).Methods We performed a retrospective observational study in which records of patients hospitalized in the ICU between June 1,2021 and June 1,2023 were reviewed.We checked the clinical,laboratory,and microbiological records of all adult patients who had carbapenem-resistant A.baumannii(CRAB)infections.Prior antibiotic treatments and definitive antibiotic treatments after culture positivity and susceptibility test results were recorded.C-reactive protein(CRP)and procalcitonin levels and leukocyte counts were noted.Length of ICU stay and 30-day mortality were defined as the outcome parameters.Results During the study period,57 patients were diagnosed with CRAB infections.The respiratory tract was the leading infection site(80.7%).In non-survivors,bloodstream infections(21.9%vs.4.0%P=0.05)and colistin-resistant(col-R)CRAB infections(43.8%vs.24.0%,P=0.12)were more common than in survivors,but these parameters were not statistically significant.The length of ICU stay was not different between survivors and non-survivors.Overall,the rate of col-R among CRAB clinical isolates was 35.1%.The 30-day mortality in all patients with CRAB infection was 56.1%.Mortality in col-R CRAB and colistin-susceptible(col-S)CRAB infections was 70.0%and 48.6%,respectively(P=0.12).Prior carbapenem use was 56.1%.Prior colistin use before col-R and col-S CRAB infections was not significant(35.0%vs.27.0%,P=0.53).Conclusions Our study provides real-world data on highly resistant A.baumannii infections and shares the characteristics of infections with such resistant strains.Unfortunately,carbapenem resistance in A.bau

关键词： Mortality Colistin-resi stant Gram-negative bacteria MDR Intensive care unit

Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

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World Journal of Hepatology 2024年第5期16卷 843-859页

作者： Michee M Bazie Mahamoudou Sanou Florencia Wendkuuni Djigma Tegwinde Rebeca Compaore Dorcas Obiri-Yeboah Benoît Kabamba Bolni Marius Nagalo Jacques Simpore Rasmata Ouédraogo department of Medicine Transmissible Diseases LaboratoryUniversitéJoseph KI-ZERBOOuagadougou 0000Burkina Faso department of Biochemistry and microbiology Molecular Biology and Genetics LaboratoryUniversity Joseph KI-ZERBOOuagadougou 0000Burkina Faso Infectious and parasitic disease Laboratory Health Sciences Research InstituteIRSS/CNRSTNational Center for Scientific and Technological ResearchOuagadougou 0000Burkina Faso department of microbiology and Immunology School of Medical SciencesUniversity of Cape CoastPMBCape Coast 0000Ghana department of Clinical biology Virology LaboratoryCliniques Universitaires Saint LucUniversitéCatholique de LouvainBruxelles 0000Belgium division of Hematology and Oncology Mayo ClinicAZ 0000United States

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including Africa.OBI can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the infection.AIM To highlight the genetic diversity and prevalence of OBI in Africa.METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa.RESULTS The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood transfusions.Cases of OBI reactivation have been reported following chemotherapy.Genotype D is the predominant,followed by genotypes A and E.CONCLUSION This review highlights the prevalence of OBI in Africa,which varies across countries and population groups.The study also demonstrates that genotype D is the most prevalent.

关键词： Occult hepatitis B infection Blood transfusion Genetic diversity

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei Zhang Yongguo Zhang Yinglin Xia Jun Sun division of Gastroenterology and Hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer Center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown VA Medical Center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 phase.Long CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized duration.Anyone infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early.People with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental models.Here,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long CovID.We highlight the potential mechanisms and possible treatment based on Gl health and microbiome.Finally,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

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

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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

Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic findings.Metastatic disease is typically associated with increased tumor diameter,multifocality,and vascular invasion.We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.CASE SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid mass.Serial CT evaluations demonstrated steatosis,but no cirrhosis or liver lesions.Endoscopic ultrasound demonstrated a normal-appearing pancreas,biliary tree,and liver.Fine needle aspiration yielded atypical cells.The differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal tumor.After review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC.Magnetic resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 hyperintensity.Alpha fetoprotein was 23.3 ng/mL.The patient was diagnosed with HCC with portocaval nodal involvement.Review:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC.We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic HCC.CONCLUSION Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary.In patients with risk factors fo

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

Unveiling a new regulator: Vacuolar V-ATPase mediates brassinosteroid signaling in Arabidopsis

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Molecular Plant 2024年第2期17卷 227-229页

作者： Shikha Malik Justin W.Walley department of Plant Pathology Entomologyand Microbiologylowa State UniversityAmesIA 50011USA

Plant growth and development are intricately regulated by hormones such as auxins,gibberellins,jamonates,cytokinins,and brassinosteroids(BRs).BRs are a group of plant steroid hormones that play a vital role in plant growth and response to the environment.BRs regulate many biological processes including cell elongation,cell division,and male fertility,as well as abiotic and biotic stress responses.

关键词： media fertility brassinosteroid

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 115-127页

作者： Yang Yi Wenzhe Li Kefang Liu Heng Xue Rong Yu Meng Zhang Yang-Oujie Bao Xinyuan Lai Jingjing Fan Yuxi Huang Jing Wang Xiaomeng Shi Junhua Li Hongping Wei Kuanhui Xiang Linjie Li Rong Zhang Xin Zhao Xue Qiao Hang Yang Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing100191China Yunnan Baiyao International Medical Research Center Peking UniversityBeijing100191China CAS Key Laboratory of pathogen microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS Key Laboratory of Special pathogens and Biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China department of microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing100191China Hubei Jiangxia Laboratory Wuhan430000China Shenzhen Children's Hospital ShenzhenGuangdong518036China

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

关键词： COVID-19 Inflammation Licorice-saponin A3 Receptor-binding domain(RBD) SARS-CoV-2

Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α

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Oncology Research 2024年第1期32卷 163-174页

作者： KUO-SHYANG JENG PO-YU CHENG YUEH-HSIEN LIN PO-CHUN LIU PING-HUI TSENG YU-CHAO WANG CHIUNG-FANG CHANG CHUEN-MIIN LEU division of General Surgery Far Eastern Memorial HospitalNew Taipei City22060Taiwan Institute of microbiology and Immunology National Yang Ming Chiao Tung UniversityTaipei City11221Taiwan Institute of Biochemistry and Molecular biology National Yang Ming Chiao Tung UniversityTaipei City11221Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung UniversityTaipei City11221Taiwan department of Medical Research Far Eastern Memorial HospitalNew Taipei City22060Taiwan

Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.

关键词： Hepatocellular carcinoma Aldo-keto reductase family member C3 Prostaglandin F2 alpha Prostaglandin F receptor