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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

Molecular Epidemiology and clinical Characteristics of Hand, Foot and Mouth Disease in North Sichuan Region, China, 2018-2023: A Descriptive Study

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Advances in microbiology 2024年第6期14卷 317-332页

作者： Zhe Xu Zheng Zhao Linming Fan Manyu Liang Jinglu Chen Jia Zeng Ping Shi Xi’en Gu Zhengdong Li Department of Pediatrics Guangyuan Central Hospital Guangyuan China Department of clinical Laboratory Guangyuan Central Hospital Guangyuan China Department of Dermatology Guangyuan Central Hospital Guangyuan China Precision Medical centre Guangyuan Central Hospital North Sichuan Regional Medical Centre Guangyuan China Department of Pulmonary and Critical Care Medicine Guangyuan Central Hospital Guangyuan China

Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.

关键词： Enterovirus HFMD Epidemiology clinical Characteristics

Antibiotic Resistance Profile of Enterococcus faecalis and Enterococcus faecium Isolates from Urine and Pleural Fluid in Two Hospitals of Cameroon

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Open Journal of Medical microbiology 2024年第1期14卷 39-49页

作者： Cécile Ingrid Djuikoue Farid Wega Grace Yemina Kombeu Cedric Seugnou Nana Christiane Possi Kiyang Lussabella Pohoko Medzam Erica Megane Noubissi Makougoum Nellie Mbianga Nkuigoua Herman Koyouo Tagne Mérimé Joël Tchinda Talokou Yvonne Valérie Yolande Mavoungou Ashu Michel Agbor microbiology Department of the Faculty of Health Sciences of the Université des Montagnes Bangangté Cameroon Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon microbiology Department of the Faculty of Health Sciences of Institut Universitaire du Golf de Guinée Douala Cameroon centre Hospitalier Dominicain St Martin de Porres Yaoundé Cameroun Faculté des Sciences de la Santé Université Marien Ngouabi Brazzaville République du Congo

Enterococcus faecalis and Enterococcus faecium rank among the leading causes of nosocomial bacteremia and urinary tract infections. They often persist on hospital surfaces due to their ability to withstand adverse environmental conditions (low or high temperatures, high pH, and high salinity). The global Enterococcus faecalis-Enterococcus faecium ratio is currently shifting towards Enterococcus faecium. Enterococci present variable levels of resistance to certain families of antibiotics. This is the case for aminoglycosides, beta-lactams and cephalosporins. In 2017, WHO ranked Enterococci among priority pathogens for research and development of new antibiotics. The objective of our study was to determine the antibiotic resistance profile of Enterococcus faecalis and Enterococcus faecium isolates from urine and pleural fluid in two hospitals in Cameroon. This cross-sectional and analytic study was carried out between June to August 2023 on hospitalized and day patients in which a cytobacteriological test of urine and pleural fluid was done. The samples were inoculated on CLED Agar for urine and on Chocolate + polyvitex and blood agar (prepared from Columbia agar) for pleural fluid samples and incubated at 37℃ for 18 to 24 hours. Identification of isolates was carried out using the API 20 STREP micro gallery (Biomerieux, France) and tested for antimicrobial susceptibility. The data on socio-demographical and potential risk factors were recorded using self-administered questionnaires and data from laboratory analyses of the specimen were collected in a data capture sheet. Potential risk factors associated with the presence of Enterococci, were evaluated using the logistic regression in univariate and multivariate analysis. P value < 0.05 was considered as significant. A total of 511 patients were recruited who were predominantly females. Enterococcus spp were isolated in 27.79% of our samples with Enterococcus faecalis mostly encountered. Enterococcus spp showed a high

关键词： Enterococcus faecalis Enterococcus faecium Healthcare-Associated Infections Antimicrobial Resistance Cameroon

Effect of pediatric Tuina on children's recurrent acute respiratory tract infections: a retrospective cohort study in Southern China

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Journal of Traditional Chinese Medicine 2024年第3期44卷 586-594页

作者： YIN Lingjia ST?LSBY LUNDBORG Cecilia WU Darong YANG Jinghua ALVESSON Helle M?lsted CAI Jianxiong LU Taoying XIE Qianwen MARRONE Gaetano Department of Global Public Health Karolinska Institutet State Key Laboratory of Dampness Syndrome of Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Outcome Assessment Research Team in Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Health Construction Administration centre Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Key Laboratory of clinical Research on Traditional Chinese Medicine Syndrome the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Department of Pediatrics the Second Affiliated Hospital of Guangzhou University of Chinese Medicine

OBJECTIVE: To determine the effectiveness of pediatric Tuina(PT) in preventing recurrent acute respiratory tract infections(ARTIs) in children. METHODS: This is a retrospective cohort study based on the electronic medical records of children with recurrent ARTIs in 2016. Children were divided into a PT group or a non-PT group, according to whether they had received PT or not in 2016. The primary outcome was the number of ARTI episodes in 2017 and 2018. The secondary outcomes were the number of ARTIs leading to outpatient department visits and outpatient antibiotic prescriptions due to ARTIs in the same time period. Negative binomial regressions were used to detect the association between PT and the outcomes. RESULTS: A total of 2303 children were included in the analysis, including 94 in the PT group and 2209 in the non-PT group. Children who received PT six or more times in 2016 had fewer episodes of ARTIs in 2017 [incidence rate ratio(IRR): 0.59, 95% confidence interval(CI)(0.42-0.84)] and 2018 [IRR: 0.58, 95% CI(0.36-0.94)] and fewer outpatient department visits due to ARTIs in 2017 [IRR: 0.56, 95% CI(0.38-0.83)] than children who had not received PT in 2016. There was no significant difference in the number of outpatient antibiotic prescriptions between the two groups. CONCLUSIONS: Receiving PT six or more times within one year is associated with a decrease in recurrent ARTIs in children in the following two years. Randomized controlled trials are needed for effect evaluation prior to establishing PT as a method for preventing recurrent ARTIs among children.

关键词： child massage pediatric Tuina respiratory tract infections

Epidemiology, clinical Features and Antifungal Resistance Profile of Candida auris in Africa: Systematic Review

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Journal of Biosciences and Medicines 2024年第1期12卷 126-149页

作者： Isidore Wendkièta Yerbanga Seydou Nakanabo Diallo Toussaint Rouamba Delwendé Florence Ouedraogo Katrien Lagrou Rita Oladele Jean-Pierre Gangneux Olivier Denis Hector Rodriguez-Villalobos Isabel Montesinos Sanata Bamba centre Hospitalier Universitaire Régional de Ouahigouya Ouahigouya Burkina Faso Ecole Doctorale des Sciences De la Santé Université Nazi Boni Bobo-Dioulasso Burkina Faso centre Muraz/Institut National de Santé Publique Bobo-Dioulasso Burkina Faso clinical Research Unit of Nanoro Institute for Research in Health Sciences National Center for Scientific and Technological Research Ouagadougou Burkina Faso Department of microbiology Immunology and Transplantation KU Leuven Leuven Belgium and Department of Laboratory Medicine and National Reference Center for Mycosis Excellence Center for Medical Mycology (ECMM) University Hospitals Leuven Leuven Belgium College of Medicine University of Lagos Lagos Nigeria Univ Rennes CHU Rennes Inserm Irset (Institut de recherche en santé environnement et travail) European ECMM Excellence Center in Medical Mycology Université de Rennes Rennes France Department of microbiology CHU Namur site-Godinne Université Catholique de Louvain Yvoir Belgium Ecole de Santé Publique Université Libre de Bruxelles Brussels Belgium Department of microbiology Cliniques Universitaires Saint-Luc—Université Catholique de Louvain Bruxelles Belgium centre Hospitalier Universitaire Sour? Sanou Bobo-Dioulasso Burkina Faso

Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.

关键词： Africa Antifungal Resistance Candida auris clinical Features Phylogenetic Clades

Is Veillonella a unique marker of physical exercise?Commentary on:

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Journal of Sport and Health Science 2024年第5期13卷 682-684页

作者： Viktor Bielik Ivan Hric Riadh Hammami Department of Biological and Medical Science Faculty of Physical Education and SportComenius University in BratislavaBratislava 81469Slovakia Department of Molecular Biology Faculty of Natural SciencesComenius University in BratislavaBratislava 84215Slovakia Biomedical Research Center Institute of Clinical and Translational ResearchSlovak Academy of SciencesBratislava 84505Slovakia School of Nutrition Sciences Faculty of Health SciencesUniversity of OttawaOttawaON K1N 6N5Canada Department of Biochemistry Microbiology and ImmunologyFaculty of MedicineUniversity of OttawaOttawaON K1N 6N5Canada

In 2020,Kostic1 published commentary on the bacterial genus Veillonella associated with the interaction between the intestinal microbiota and skeletal *** then,novel perspectives on the bidirectional gut-muscle communication axis have gained a lot of *** purpose of this commentary is to explore some of the challenging issues presented in Scheiman et al.

关键词： skeletal gained

Ability of Helicobacter pylori to internalize into Candida

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World Journal of Gastroenterology 2024年第16期30卷 2281-2284页

作者： Zheng-Hong Chen Jian-Chao Sun Ting-Xiu Yang Gu-Zhen Cui Key Laboratory of microbiology and Parasitology of Education Department of Guizhou Guizhou Medical UniversityGuiyang 561113Guizhou ProvinceChina Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education Guizhou Medical UniversityGuiyang 561113Guizhou ProvinceChina Joint Laboratory of Helicobacter Pylori and Intestinal Microecology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550009Guizhou ProvinceChina Department of Quality Control Guizhou Provincial Center for Clinical LaboratoryGuiyang 550002Guizhou ProvinceChina Department of Hospital Infection and Management Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina

The following are our views regarding the“letter to the editor”(Helicobacter is preserved in yeast vacuoles!Does Koch’s postulates confirm it?)by Alipour and Gaeini,and the response“letter to the editor”(Candida accommodates nonculturable Helicobacter pylori in its vacuole-Koch’s postulates aren’t applicable)by Siavoshi and *** and Gaeini rejected the methods,results,discussion,and conclusions summarized in a review article by Siavoshi and *** present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori(***)to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse,transporting potentially infectious *** into the stomach of humans.

关键词： Helicobacter pylori Candida yeast Intracellular presence Helicobacter pylori-specific gene Helicobacter pylori transmission

Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： Ke-Gang Linghu Tian Zhang Guang-Tao Zhang Peng Lv Wen-Jun Zhang Guan-Ding Zhao Shi-Hang Xiong Qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu Chang-Sheng Zhang Hua Yu State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Macao centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State Key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory ***,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been ***(DNQ)is a natural small molecule discovered from marine *** current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of *** exhibited significant anti-inflammatory properties both in vitro and in *** pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and *** exerted anti-inflammatory effects through activation of Nrf2/ARE ***1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving *** specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass *** triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of *** findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target Keap1/Nrf2 Alkylation Ubiquitination

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

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Advances in microbiology 2024年第5期14卷 247-255页

作者： Pooja Patel Yogita Mistry Monika Patel Summaiya Mullan Viral Research and Diagnostic Laboratory Department of Microbiology Government Medical college Surat India

Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided qu

关键词： SARS-CoV-2 S Gene Target Failure Whole Genome Sequencing Omicron