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Physicochemical properties, molecular structure, antioxidant activity, and biological function of extracellular melanin from Ascosphaera apis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第5期23卷 365-381页

作者： Zhi LI Hui HENG Qiqian QIN Lanchun CHEN Yuedi WANG Zeyang ZHOU College of Life Sciences Chongqing Normal UniversityChongqing 401331China Chongqing Key Laboratory of Vector Insects Chongqing 401331China Chongqing Key Laboratory of Animal biology Chongqing 401331China Chongqing Key Laboratory of Microsporidia infection and Control Chongqing 400715China The State Key Laboratory of Silkworm Genome biology Southwest UniversityChongqing 400715China

Ascosphaera apis spores containing a dark-colored pigment infect honeybee larvae,resulting in a large-scale collapse of the bee colony due to chalkbrood disease.However,little is known about the pigment or whether it plays a role in bee infection caused by A.apis.In this study,the pigment was isolated by alkali extraction,acid hydrolysis,and repeated precipitation.Ultraviolet(UV)analysis revealed that the pigment had a color value of 273,a maximum absorption peak at 195 nm,and a high alkaline solubility(7.67%)and acid precipitability.Further chemical structure analysis of the pigment,including elemental composition,Fourier transform infrared(FTIR)spectroscopy,Raman spectroscopy,mass spectrometry,and nuclear magnetic resonance(NMR),proved that it was a eumelanin with a typical indole structure.The molecular formula of melanin is C10H6O4N2,and its molecular weight is 409 Da.Melanin has hydroxyl,carboxyl,amino,and phenolic groups that can potentially chelate to metal ions.Antioxidant function analyses showed that A.apis melanin had a high scavenging activity against superoxide,hydroxyl,and 2,2-diphenyl-1-picrylhydrazyl(DPPH)radicals,and a high reducing ability to Fe3+.Indirect immunofluorescence assay(IFA),scanning electron microscopy(SEM),and transmission electron microscopy(TEM)analyses showed that A.apis melanin was located on the spore wall.The spore wall localization,antioxidant activity,and metal ion chelating properties of fungal melanin have been suggested to contribute to spore pathogenicity.However,further infection experiments showed that melanin-deficient spores did not reduce the mortality of bee larvae,indicating that melanin does not increase the virulence of A.apis spores.This study is the first report on melanin produced by A.apis,providing an important background reference for further study on its role in A.apis.

关键词： Melanin Molecular structure Antioxidant activity Subcellular localization Ascosphaera apis

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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang Lingli Wang Yibo Ding Renxian Tang Xiucheng Pan Kuiyang Zheng Luc J.Wvan der Laan Qiuwei Pan Wenshi Wang Department of Pathogen biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed patients.However,there are still unmet needs for treating chronic HEV infections.Herein,we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds.Upon screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities.Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection.Pyrazofurin selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV strains.Encouragingly,both drugs exhibited a sizeable therapeutic window against HEV.For instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in patients.Mechanistically,their anti-HEV mode of action depends on the blockage of pyrimidine synthesis.Notably,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral activity.In conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV infections.Based on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

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B-cell and antibody responses to SARS-CoV-2:infection,vaccination,and hybrid immunity

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Cellular & Molecular Immunology 2024年第2期21卷 144-158页

作者： Dennis Lapuente Thomas H.Winkler Matthias Tenbusch Institut für klinische und molekulare Virologie Universitätsklinikum Erlangen und Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossgarten 491054 ErlangenGermany Department of biology Division of GeneticsNikolaus-Fiebiger-Center for Molecular MedicineFriedrich-Alexander-Universität Erlangen-Nürnberg(FAU)ErlangenGermany Medical Immunology Campus Erlangen Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossplatz 191054 ErlangenGermany

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

关键词： SARS-CoV-2 neutralizing antibodies memory responses vaccines IgG4

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Periodontitis:An often-neglected complication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： Marina G Kudiyirickal Joseph M Pappachan Primary Care Dental Practice The Smile ClinicPreston PR16PZUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The bidirectional association between type 2 diabetes mellitus(T2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular disease.DM can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal disease.On the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of T2DM.Periodontitis if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with T2DM.The prevalence of periodontitis was found to be 75.7%in this study.Based on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2DM patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.

关键词： Diabetes mellitus Periodontitis Predictive factors Cardiovascular disease Glycaemic control

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Ultrastable graphene isolated Au Ag nanoalloy for SERS biosensing and photothermal therapy of bacterial infection

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Chinese Chemical Letters 2024年第3期35卷 198-203页

作者： Shengkai Li Zhiyang Li Qing Hao Shen Wang Yanxia Yang Jieqiong Xu Zhiwei Yin Liang Zhang Zhuo Chen Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China School of Chemistry and Chemical Engineering/Guangzhou Key Laboratory for Clean Energy and Materials/Key Laboratory for Water Quality and Conservation of the Pearl River Delta Ministry of EducationGuangzhou UniversityGuangzhou 510006China

Plasmonic metal nanomaterials with intrinsic surface–enhanced Raman scattering(SERS)and photothermal properties,especially AuAg nanoalloys with both the outstanding merits of Au and Ag nanocrystals,show huge application prospects in bacterial theranostics.However,the direct exposure of AuAg nanoalloys in external conditions probably cause undesirable reactions and poisonous metal ion leakage during SERS detection and photothermal antibacterial therapy process,which severely hinder bacterial theranostics applications.Herein,we report an ultrastable graphene–isolated AuAg nanoalloy(GAA)with AuAg core confined in few–layer graphitic shell as a versatile platform for bacterial detection and therapy.The encapsulation of graphene ensures the good stability of AuAg core,that its superior SERS and photothermal properties are therefore further guaranteed.GAA is used for SERS detection of two vital bacterial biomarkers(including corrosive cyanide and pyocyanin),exhibiting good SERS quantitative and multiplexing ability.GAA is further used for photothermal antibacterial therapy application,and ultrahigh antibacterial efficacies for both Gram–negative Escherichia coli and Gram–positive Staphylococcus aureus are achieved under 808 nm laser irradiation.This work proposes a valuable method to develop robust bacterial theranostic platform.

关键词： Localized surface plasmon resonance Graphitic shell isolated AuAg nanoalloy(GAA) Surface–enhanced Raman scattering(SERS) Bacterial biomarker detection Photothermal antibacterial therapy

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Screening and identifying natural products with SARS-CoV-2 infection inhibitory activity from medicinal fungi

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Biosafety and Health 2024年第1期6卷 12-20页

作者： Shuang Zhao Amelia Siqi Huang Weibo Zhang Lili Ren Hexiang Wang Jianbin Wang Xinyang Shao Guanbo Wang Institute of Agri-Food Processing and Nutrition Institute of Plant ProtectionBeijing Academy of Agriculture and Forestry SciencesBejing 100097China Bejing Key Laboratory of Fruits and Vegetable Storage and Processing Key Laboratory of Vegetable Postharvest ProcessingMinistry of AgricultureBejing 100097China Dalton Academy The Affliated High School of Peking UniversityBeijing 100190China NHC Key Laboratory of Systems biology of Pathogens and Christophe Merieux Laboratory National Institute of Pathogen BiologyBejing 100730China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China College of Biological Sciences China Agricultural UniversityBejing 100193China School of Life Sciences Tsinghua UniversityBeijing 100084China Changping Laboratory Beijing 102206China Institute for Cell Analysis Shenzhen Bay LaboratoryShenzhen 518132China

The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative measures,pharmaceutical intervention is also crucial.Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS‐CoV‐2 and other coronaviruses.In this study,we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels,as well as molecular separation and characterization,to screen and identify natural products with antiviral activity.Using this workflow,we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods.We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS‐CoV‐2 infection and receptor binding domain‐human angiotensin‐converting enzyme 2(RBD‐hACE2)binding in vitro.Following charge‐and size‐based characterization of the active compounds through filtration and chromatographic fractionation,mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition.Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID‐19 and other diseases.

关键词： Medicinal fungi Natural products Antiviral activity COVID‐19 Polysaccharides

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Bile acids and coronavirus disease 2019

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1939-1950页

作者： Xiaoru Huang Xuening Liu Zijian Li Department of Pharmacy Peking University Third HospitalBeijing 100191China Department of Pharmaceutical Management and Clinical Pharmacy College of PharmacyPeking UniversityBeijing 100191China Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalBeijing Key Laboratory of Cardiovascular Receptors ResearchKey Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesMinistry of HealthState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has been significantly alleviated.However,long-term health effects and prevention strategy remain unresolved.Thus,it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 infection.Emerging research indicates a link between COVID-19 and bile acids,traditionally known for facilitating dietary fat absorption.The bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor,a bile acid nuclear receptor.The activation of G-protein-coupled bile acid receptor,another membrane receptor for bile acids,has also been found to regulate the expression of angiotensin-converting enzyme 2,the receptor through which the virus enters human cells.Here,we review the latest basic and clinical evidence linking bile acids to SARS-CoV-2,and reveal their complicated pathophysiological mechanisms.

关键词： Bile acids COVID-19 Farnesoid X receptor G-protein-coupled bile acid receptor SARS-CoV-2 Angiotensin-converting enzyme 2 Ursodeoxycholic acid Chenodeoxycholic acid

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Establishment of a transformation system in close relatives of wheat under the assistance of TaWOX5

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Journal of Integrative Agriculture 2024年第6期23卷 1839-1849页

作者： Yanan Chang Junxian Liu Chang Liu Huiyun Liu Huali Tang Yuliang Qiu Zhishan Lin Ke Wang Yueming Yan Xingguo Ye Institute of Crop Sciences Chinese Academy of Agricultural SciencesBeijing 100081China Beijing Key Laboratory of Plant Gene Resources and Biotechnology for Carbon Reduction and Environment Improvement/College of Life Science Capital Normal UniversityBeijing 100048China College of Agronomy and Biotechnology China Agricultural UniversityBeijing 100193China State Key Laboratory of Plant Cell and Chromosome Engineering/Institute of Genetics and Developmental biology Chinese Academy of SciencesBeijing 100101China

Species closely related to wheat are important genetic resources for agricultural production,functional genomics studies and wheat improvement.In this study,a wheat gene related to regeneration,TaWOX5,was applied to establish the Agrobacterium-mediated transformation systems of Triticum monococcum,hexaploid triticale,and rye(Secale cereale L.)using their immature embryos.Transgenic plants were efficiently generated.During the transformation process,the Agrobacterium infection efficiency was assessed by histochemical staining forβ-glucuronidase(GUS).Finally,the transgenic nature of regenerated plants was verified by polymerase chain reaction(PCR)-based genotyping for the presence of the GUS and bialaphos resistance(bar)genes,histochemical staining for GUS protein,and the QuickStix strip assay for bar protein.The transformation efficiency of T.monococcum genotype PI428182 was 94.4%;the efficiencies of four hexaploid triticale genotypes Lin456,ZS3297,ZS1257,and ZS3224 were 52.1,41.2,19.4,and 16.0%,respectively;and the transformation efficiency of rye cultivar Lanzhou Heimai was 7.8%.Fluorescence in situ hybridization(FISH)and genomic in situ hybridization(GISH)analyses indicated that the GUS transgenes were integrated into the distal or near centromere(proximal)regions of the chromosomes in transgenic T.monococcum and hexaploid triticale plants.In the transgenic hexaploid triticale plants,the foreign DNA fragment was randomly integrated into the AABB and RR genomes.Furthermore,the transgene was almost stably inherited in the next generation by Mendel’s law.The findings in this study will promote the genetic improvement of the three plant species for grain or forage production and the improvement of cereal species including wheat for functional genomics studies.

关键词： Triticum monococcum hexaploid triticale rye TaWOX5 Agrobacterium transformation efficiency

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Knock-out of BnHva22c reduces the susceptibility of Brassica napus to infection with the fungal pathogen Verticillium longisporum

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The Crop Journal 2024年第2期12卷 503-514页

作者： Wanzhi Ye Roxana Hossain Michael Prbsting Abdallah Abdelmegid Mohamed Ali Lingyue Han Ying Miao Steffen Rietz Daguang Cai Dirk Schenke Department of Molecular Phytopathology and Biotechnology Institute of PhytopathologyChristian-Albrechts-University of KielKielGermany Institut für Zuckerrübenforschung GöttingenGermany Plant Pathology Department Faculty of Agriculture and Natural ResourcesAswan UniversityAswanEgypt Fujian Provincial Key Laboratory of Plant Functional biology College of Life SciencesFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Hohenlieth-Hof NPZ Innovation GmbHHoltseeGermany

Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control this disease.Here,we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance.Hva22c is a member of the Hva22 gene family,originally described for barley(Hordeum vulgare).Several Hva22 members have been located at the endoplasmic reticulum.Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR.We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’susceptibility to Vl43 infection and impaired the development of disease symptoms.To understand the underlying mechanism,we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants.We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi.Significantly,a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems.Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type.These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction.Its loss of function reduces plant susceptibility,most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses.These findings can help improve OSR resistance to V.longisporum infection.

关键词： Hva22c Susceptibility factor CRISPR/Cas9 Brassica napus Arabidopsis Verticillium longisporum Resistance breeding

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Combatting anthrax outbreaks across Nigeria's national land borders: need to optimize surveillance with epidemiological surveys

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Infectious Diseases of Poverty 2024年第1期13卷 100-100页

作者： Hammed O.Mogaji Babatunde Adewale Stella I.Smith Ehimario U.Igumbor Chidumebi J.Idemili Andrew W.Taylor-Robinson Yale School of Public Health Yale University New Haven USA Parasitology and Epidemiology unit Federal University Oye-Ekiti Oye-Ekiti Nigeria Department of Public Health and Epidemiology Nigerian Institute of Medical Research Lagos Nigeria Department of Molecular biology and Biotechnology Nigerian Institute of Medical Research Lagos Nigeria Centre for Infectious Disease Research Nigerian Institute of Medical Research Lagos Nigeria Department of Public Health Walter Sisulu University Mthatha South Africa Institute of Health Policy Management and Evaluation University of Toronto Toronto Canada College of Health Sciences Vin University Hanoi Vietnam Center for Global Health Perelman School of Medicine University of Pennsylvania Philadelphia USA

Background Anthrax is a non-contagious zoonotic disease caused by the Gram-positive,spore-forming bac-terium Bacillus anthracis.infection is common in livestock and wild animals such as cattle,goats,sheep,camels,and antelopes.In humans,anthrax may occur after contact with contaminated carcasses or animal products like milk and meat.The best method to prevent anthrax in people is to ensure livestock are vaccinated,which significantly limits the risk of zoonotic spread to humans.However,the rate of vaccination of domesticated animals kept by nomadic pastoralists in West Africa is low.These groups regularly cross over national boundaries with their grazing herds.Nigeria is a country that historically has done comparatively well to contain this public health threat.However,in 2023 several outbreaks of human disease appear linked to the consumption of anthrax-contaminated animal products brought into Nigeria by pastoralists from neighboring countries.Clinical manifestations include skin sores or ulcers,nausea,vomiting,and fever.This article aims to raise awareness of recent outbreaks of anthrax in West Africa and to callfor a renewed focus on measures to combat this neglected public health concern to the region.Main body The imperative to pinpoint pivotal issues relating to the ongoing emergence of anthrax cases in Nigeria cannot be overstated.By delving into the prevalence of anthrax in both livestock and human populations residing along Nigeria's borders,unraveling the genetic diversity and potential sources of B.anthracis strains,and identify-ing the primary animal host(s)responsible for transmission,we stand to enhance our understanding of this critical issue.Furthermore,investigating the multifaceted factors contributing to anthrax transmission,assessing community knowledge and practices,mapping common migratory routes of pastoralists,and formulating targeted interven-tion strategies tailored to the challenges of border communities,are each crucial steps towards effective control andprevention.Conclusion Closing

关键词： border Combat doubt

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