The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progressIn this work based on 78 gastritis patients an...The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progressIn this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrenee and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.展开更多
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter （ASBT） （also referred to as Ibat; gene nam...Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter （ASBT） （also referred to as Ibat; gene name Slc10a2） is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified （t-ASBT, multidrug resistance （MDR）3, an unidentified anion exchanger system and organic solute transporter （Ost） heteromeric transporter, Ostα- Ostβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliary plexus back to hepatocytes for re-secretion into bile. This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3＇, 5＇monophosphate （cAMP）-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines. Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C （PKC）, phosphoinositide 3-kinase （PI3K）, mitogenactivated protein （MAP） kinase and extracellular signalregulated protein kinase （ERK） intracellular signals. Bile acids significantly alter cholangiocyte secretion,proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals,and in some instances trigger opposing effects on cholangiocyte secretion, prolife展开更多
Fluorescence polarization microscopy(FPM)aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy.Conventional FPM often ...Fluorescence polarization microscopy(FPM)aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy.Conventional FPM often suffers from the presence of a large number of molecules within the diffraction-limited volume,with averaged fluorescence polarization collected from a group of dipoles with different orientations.Here,we apply sparse deconvolution and least-squares estimation to fluorescence polarization modulation data and demonstrate a super-resolution dipole orientation mapping(SDOM)method that resolves the effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area.We further apply this method to resolve structural details in both fixed and live cells.For the first time,we show that different borders of a dendritic spine neck exhibit a heterogeneous distribution of dipole orientation.Furthermore,we illustrate that the dipole is always perpendicular to the direction of actin filaments in mammalian kidney cells and radially distributed in the hourglass structure of the septin protein under specific labelling.The accuracy of the dipole orientation can be further mapped using the orientation uniform factor,which shows the superiority of SDOM compared with its wide-field counterpart as the number of molecules is decreased within the smaller focal area.Using the inherent feature of the orientation dipole,the SDOM technique,with its fast imaging speed(at sub-second scale),can be applied to a broad range of fluorescently labeled biological systems to simultaneously resolve the valuable dipole orientation information with super-resolution imaging.展开更多
This paper is a compilation of notes on 142 fungal taxa,including five new families,20 new genera,and 100 new species,representing a wide taxonomic and geographic range.The new families,Ascocylindricaceae,Caryosporace...This paper is a compilation of notes on 142 fungal taxa,including five new families,20 new genera,and 100 new species,representing a wide taxonomic and geographic range.The new families,Ascocylindricaceae,Caryosporaceae and Wicklowiaceae(Ascomycota)are introduced based on their distinct lineages and unique morphology.The new Dothideomycete genera Pseudomassariosphaeria(Amniculicolaceae),Heracleicola,Neodidymella and Pseudomicrosphaeriopsis(Didymellaceae),Pseudopithomyces(Didymosphaeriaceae),Brunneoclavispora,Neolophiostoma and Sulcosporium(Halotthiaceae),Lophiohelichrysum(Lophiostomataceae),Galliicola,Populocrescentia and Vagicola(Phaeosphaeriaceae),Ascocylindrica(Ascocylindricaceae),Elongatopedicellata(Roussoellaceae),Pseudoasteromassaria(Latoruaceae)and Pseudomonodictys(Macrodiplodiopsidaceae)are introduced.The newly described species of Dothideomycetes(Ascomycota)are Pseudomassariosphaeria bromicola(Amniculicolaceae),Flammeascoma lignicola(Anteagloniaceae),Ascocylindrica marina(Ascocylindricaceae),Lembosia xyliae(Asterinaceae),Diplodia crataegicola and Diplodia galiicola(Botryosphaeriaceae),Caryospora aquatica(Caryosporaceae),Heracleicola premilcurensis and Neodidymella thailandicum(Didymellaceae),Pseudopithomyces palmicola(Didymosphaeriaceae),Floricola viticola(Floricolaceae),Brunneoclavispora bambusae,Neolophiostoma pigmentatum and Sulcosporium thailandica(Halotthiaceae),Pseudoasteromassaria fagi(Latoruaceae),Keissleriella dactylidicola(Lentitheciaceae),Lophiohelichrysum helichrysi(Lophiostomataceae),Aquasubmersa japonica(Lophiotremataceae),Pseudomonodictys tectonae(Macrodiplodiopsidaceae),Microthyrium buxicola and Tumidispora shoreae(Microthyriaceae),Alloleptosphaeria clematidis,Allophaeosphaeria cytisi,Allophaeosphaeria subcylindrospora,Dematiopleospora luzulae,Entodesmium artemisiae,Galiicola pseudophaeosphaeria,Loratospora luzulae,Nodulosphaeria senecionis,Ophiosphaerella aquaticus,Populocrescentia forlicesenensis and Vagicola vagans(Phaeosphaeriaceae),Elongatopedicellata lignicola,Roussoella magnatum an展开更多
AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response(UPR) in hepatitis B(HBV) and C(HCV) infected hepatocytes.METHODS: We performed immunofluorescence confocal microscopy on 10 l...AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response(UPR) in hepatitis B(HBV) and C(HCV) infected hepatocytes.METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP(GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. AntiHCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy(LC3β punctuate), apoptosis(cleaved caspase-3), and unfolded protein response(GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows(Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent noninfected cells.RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase(P < 0.001) in apoptosis(cleavage of caspase-3), autophagy(LC3β punctate), and UPR(increase in GRP78 expression) in the HCV- and HBVinfected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBV^(Neg) and HBV^(Pos) revealed that majority of HBVinfected hepatocytes display strong positive stainingfor LC3β. Interestingly, although XBP splicing in HBVinfected cells was significantly higher(P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells(P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR.CONCLUSION: The results of this stu展开更多
Notes on 113 fungal taxa are compiled in this paper,including 11 new genera,89 new species,one new subspecies,three new combinations and seven reference specimens.Awide geographic and taxonomic range of fungal taxa ar...Notes on 113 fungal taxa are compiled in this paper,including 11 new genera,89 new species,one new subspecies,three new combinations and seven reference specimens.Awide geographic and taxonomic range of fungal taxa are detailed.In the Ascomycota the new genera Angustospora(Testudinaceae),Camporesia(Xylariaceae),Clematidis,Crassiparies(Pleosporales genera incertae sedis),Farasanispora,Longiostiolum(Pleosporales genera incertae sedis),Multilocularia(Parabambusicolaceae),Neophaeocryptopus(Dothideaceae),Parameliola(Pleosporales genera incertae sedis),and Towyspora(Lentitheciaceae)are introduced.Newly introduced species are Angustospora nilensis,Aniptodera aquibella,Annulohypoxylon albidiscum,Astrocystis thailandica,Camporesia sambuci,Clematidis italica,Colletotrichum menispermi,C.quinquefoliae,Comoclathris pimpinellae,Crassiparies quadrisporus,Cytospora salicicola,Diatrype thailandica,Dothiorella rhamni,Durotheca macrostroma,Farasanispora avicenniae,Halorosellinia rhizophorae,Humicola koreana,Hypoxylon lilloi,Kirschsteiniothelia tectonae,Lindgomyces okinawaensis,Longiostiolum tectonae,Lophiostoma pseudoarmatisporum,Moelleriella phukhiaoensis,M.pongdueatensis,Mucoharknessia anthoxanthi,Multilocularia bambusae,Multiseptospora thysanolaenae,Neophaeocryptopus cytisi,Ocellularia arachchigei,O.ratnapurensis,Ochronectria thailandica,Ophiocordyceps karstii,Parameliola acaciae,P.dimocarpi,Parastagonospora cumpignensis,Pseudodidymosphaeria phlei,Polyplosphaeria thailandica,Pseudolachnella brevifusiformis,Psiloglonium macrosporum,Rhabdodiscus albodenticulatus,Rosellinia chiangmaiensis,Saccothecium rubi,Seimatosporium pseudocornii,S.pseudorosae,Sigarispora ononidis and Towyspora aestuari.New combinations are provided for Eutiarosporella dactylidis(sexual morph described and illus trated)and Pseudocamarosporium pini.Descriptions,illustrations and/or reference specimens are designated for Aposphaeria corallinolutea,Cryptovalsa ampelina,Dothiorella vidmadera,Ophiocordyceps formosana,Petrakia echinata,Phragmoporthe conformis and Pse展开更多
The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for t...The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors （ER-α） and （ER-β） subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades JERK1/2 （extracellular regulated kinases 1/2, PI3-kinase/AKT （phosphatidylinositol-3＇ kinase/AKT）] typical of growth factors such as insulin like growth factor （IGF1）, nerve growth factor （NGF） and vascular endothelial growth factor （VEGF）, thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.展开更多
Ebola virus （EBOV） causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein （GP...Ebola virus （EBOV） causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein （GP） mediates widespread inflammation and cellular damage, these changes have mainly focused on alterations at the protein level, the role of microRNAs （miRNAs） in the molecular pathogenesis underlying this lethal disease is not fully understood. Here, we report that the miRNAs hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells （HUVECs） following expression of EBOV GP. Among the proteins encoded by predicted targets of these miRNAs, the adhesion-related molecules tissue factor pathway inhibitor （TFPI）, dystroglycan! （DAG1） and the caspase 8 and FADD-like apoptosis regulator （CFLAR） were significantly downregulated in EBOV GP-expressing HUVECs. Moreover, inhibition of hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p, or overexpression of TFPI, DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP. Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.展开更多
Taxonomic names are key links between various databases that store information on different organisms.Several global fungal nomenclural and taxonomic databases(notably Index Fungorum,Species Fungorum and MycoBank)can ...Taxonomic names are key links between various databases that store information on different organisms.Several global fungal nomenclural and taxonomic databases(notably Index Fungorum,Species Fungorum and MycoBank)can be sourced to find taxonomic details about fungi,while DNA sequence data can be sourced from NCBI,EBI and UNITE databases.Although the sequence data may be linked to a name,the quality of the metadata is variable and generally there is no corresponding link to images,descriptions or herbarium material.There is generally no way to establish the accuracy of the names in these genomic databases,other than whether the submission is from a reputable source.To tackle this problem,a new database(FacesofFungi),accessible at www.facesoffungi.org(FoF)has been established.This fungal database allows deposition of taxonomic data,phenotypic details and other useful data,which will enhance our current taxonomic understanding and ultimately enable mycologists to gain better and updated insights into the current fungal classification system.In addition,the database will also allow access to comprehensive metadata including descriptions of voucher and type specimens.This database is user-friendly,providing links and easy access between taxonomic ranks,with the classification system based primarily on molecular data(from the literature and via updated web-based phylogenetic trees),and to a lesser extent on morphological data when molecular data are unavailable.In FoF species are not only linked to the closest phylogenetic representatives,but also relevant data is provided,wherever available,on various applied aspects,such as ecological,industrial,quarantine and chemical uses.The data include the three main fungal groups(Ascomycota,Basidiomycota,Basal fungi)and fungus-like organisms.The FoF webpage is an output funded by the Mushroom Research Foundation which is an NGO with seven directors with mycological expertise.The webpage has 76 curators,and with the help of these specialists,FoF will provide an updated natural c展开更多
Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologie...Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologies due to excessive inflammation.Professional phagocytes such as neutrophils(PMNs),eosinophils,monocytes,and macrophages use superoxide-generating NADPH oxidase(NOX)as part of their arsenal of antimicrobial mechanisms to produce high levels of ROS.NOX is a multisubunit enzyme complex composed of five essential subunits,two of which are localized in the membrane,while three are localized in the cytosol.In resting phagocytes,the oxidase complex is unassembled and inactive;however,it becomes activated after cytosolic components translocate to the membrane and are assembled into a functional oxidase.The NOX isoforms play a variety of roles in cellular differentiation,development,proliferation,apoptosis,cytoskeletal control,migration,and contraction.Recent studies have identified NOX as a major contributor to disease pathologies,resulting in a shift in focus on inhibiting the formation of potentially harmful free radicals.Therefore,a better understanding of the molecular mechanisms and the transduction pathways involved in NOX-mediated signaling is essential for the development of new therapeutic agents that minimize the hyperproduction of ROS.The current review provides a thorough overview of the various NOX enzymes and their roles in disease pathophysiology,highlights pharmacological strategies,and discusses the importance of computational modeling for future NOX-related studies.展开更多
Nonalcoholic fatty liver disease （NAFLD）, an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to li...Nonalcoholic fatty liver disease （NAFLD）, an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.展开更多
This is a continuity of a series of taxonomic and phylogenetic papers on the fungi where materials were collected from many countries,examined and described.In addition to extensive morphological descriptions and appr...This is a continuity of a series of taxonomic and phylogenetic papers on the fungi where materials were collected from many countries,examined and described.In addition to extensive morphological descriptions and appropriate asexual and sexual connections,DNA sequence data are also analysed from concatenated datasets to infer phylogenetic relationships and substantiate systematic positions of taxa within appropriate ranks.Wherever new species or combinations are proposed,we apply an integrative approach using morphological and molecular data as well as ecological features wherever applicable.Notes on 112 fungal taxa are compiled in this paper including Biatriosporaceae and Roussoellaceae,Didysimulans gen.nov.,81 new species,18 new host records and new country records,five reference specimens,two new combinations,and three sexual and asexual morph reports.The new species are Amanita cornelii,A.emodotrygon,Angustimassarina alni,A.arezzoensis,A.italica,A.lonicerae,A.premilcurensis,Ascochyta italica,A.rosae,Austroboletus appendiculatus,Barriopsis thailandica,Berkleasmium ariense,Calophoma petasitis,Camarosporium laburnicola,C.moricola,C.grisea,C.ossea,C.paraincrustata,Colletotrichum sambucicola,Coprinopsis cerkezii,Cytospora gelida,Dacrymyces chiangraiensis,Didysimulans italica,D.mezzanensis,Entodesmium italica,Entoloma magnum,Evlachovaea indica,Exophiala italica,Favolus gracilisporus,Femsjonia monospora,Fomitopsis flabellata,F.roseoalba,Gongronella brasiliensis,Helvella crispoides,Hermatomyces chiangmaiensis,H.chromolaenae,Hysterium centramurum,Inflatispora caryotae,Inocybe brunneosquamulosa,I.luteobrunnea,I.rubrobrunnea,Keissleriella cirsii,Lepiota cylindrocystidia,L.flavocarpa,L.maerimensis,Lophiotrema guttulata,Marasmius luculentus,Morenoina calamicola,Moelleriella thanathonensis,Mucor stercorarius,Myrmecridium fluviae,Myrothecium septentrionale,Neosetophoma garethjonesii,Nigrograna cangshanensis,Nodulosphaeria guttulatum,N.multiseptata,N.sambuci,Panus subfasciatus,Paraleptosphaeria padi,Paraphaeosphaeri展开更多
Realizing personalized medicine requires integrating diverse data types with bioinformatics.The most vital data are genomic information for individuals that are from advanced next-generation sequencing(NGS) technologi...Realizing personalized medicine requires integrating diverse data types with bioinformatics.The most vital data are genomic information for individuals that are from advanced next-generation sequencing(NGS) technologies at present.The technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the data.The prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work alike.Bioinformatics is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized medicine.We review some key bioinformatics tasks,issues,and challenges in contexts of IT requirements,data quality,analysis tools and pipelines,and validation of biomarkers.展开更多
Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most mal...Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.展开更多
Cancer stem cell （CSC） theory suggests a cell-lineage structure in tumor cells in which CSCs are capable of giving rise to the other non-stem cancer cells （NSCCs） but not vice versa. However, an alternative scenar...Cancer stem cell （CSC） theory suggests a cell-lineage structure in tumor cells in which CSCs are capable of giving rise to the other non-stem cancer cells （NSCCs） but not vice versa. However, an alternative scenario of bidirectional interconversions between CSCs and NSCCs was proposed very recently. Here we present a general population model of cancer cells by integrating conventional cell divisions with direct conversions between different cell states, namely, not only can CSCs differentiate into NSCCs by asymmetric cell division, NSCCs can also dedifferentiate into CSCs by cell state conversion. Our theoretical model is validated when applying the model to recent experimental data. It is also found that the transient increase in CSCs proportion initiated from the purified NSCCs subpopulation cannot be well predicted by the conventional CSC model where the conversion from NSCCs to CSCs is forbidden, implying that the cell state conversion is required especially for the transient dynamics. The theoretical analysis also gives the condition such that our general model can be equivalently reduced into a simple Markov chain with only cell state transitions keeping the same cell proportion dynamics.展开更多
Single-cell RNA sequencing(scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell subpopulations and lineages, with an effe...Single-cell RNA sequencing(scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell subpopulations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data(VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.展开更多
Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularit...Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.展开更多
Decades of research in glial biology have investigated mechanisms of neuro-glial interplay,demonstrating that neurons and glia intimately cooperate for energy metabolism in the central nervous system(CNS)(Magistretti ...Decades of research in glial biology have investigated mechanisms of neuro-glial interplay,demonstrating that neurons and glia intimately cooperate for energy metabolism in the central nervous system(CNS)(Magistretti and Allaman,2018).展开更多
BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unkno...BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.展开更多
基金National Natural Science Foundation of China (Grant Nos. 81630103, 91729301, 91229201 and 81225025)the Project of Tsinghua-Fuzhou Insititute for Data Technology (TFIDT2018001)to S. Li and grants 61673231 and 61721003 to X. Zhang.
文摘The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progressIn this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrenee and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+9 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA14
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金a NIH grant DK54208 to Gene LeSage, and a VA Research Scholar Award, a VA Merit Award and the NIH grants DK58411 and DK062975 to Gianfranco Alpini
文摘Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter （ASBT） （also referred to as Ibat; gene name Slc10a2） is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified （t-ASBT, multidrug resistance （MDR）3, an unidentified anion exchanger system and organic solute transporter （Ost） heteromeric transporter, Ostα- Ostβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliary plexus back to hepatocytes for re-secretion into bile. This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3＇, 5＇monophosphate （cAMP）-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines. Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C （PKC）, phosphoinositide 3-kinase （PI3K）, mitogenactivated protein （MAP） kinase and extracellular signalregulated protein kinase （ERK） intracellular signals. Bile acids significantly alter cholangiocyte secretion,proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals,and in some instances trigger opposing effects on cholangiocyte secretion, prolife
基金supported by the National Key Basic Research Program(973 Program,2012CB316503)the National Instrument Development Special Program(2013YQ03065102)+1 种基金the National Natural Science Foundation of China(31361163004,31327901,61475010 and 61428501)supported by UTD funds.
文摘Fluorescence polarization microscopy(FPM)aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy.Conventional FPM often suffers from the presence of a large number of molecules within the diffraction-limited volume,with averaged fluorescence polarization collected from a group of dipoles with different orientations.Here,we apply sparse deconvolution and least-squares estimation to fluorescence polarization modulation data and demonstrate a super-resolution dipole orientation mapping(SDOM)method that resolves the effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area.We further apply this method to resolve structural details in both fixed and live cells.For the first time,we show that different borders of a dendritic spine neck exhibit a heterogeneous distribution of dipole orientation.Furthermore,we illustrate that the dipole is always perpendicular to the direction of actin filaments in mammalian kidney cells and radially distributed in the hourglass structure of the septin protein under specific labelling.The accuracy of the dipole orientation can be further mapped using the orientation uniform factor,which shows the superiority of SDOM compared with its wide-field counterpart as the number of molecules is decreased within the smaller focal area.Using the inherent feature of the orientation dipole,the SDOM technique,with its fast imaging speed(at sub-second scale),can be applied to a broad range of fluorescently labeled biological systems to simultaneously resolve the valuable dipole orientation information with super-resolution imaging.
文摘This paper is a compilation of notes on 142 fungal taxa,including five new families,20 new genera,and 100 new species,representing a wide taxonomic and geographic range.The new families,Ascocylindricaceae,Caryosporaceae and Wicklowiaceae(Ascomycota)are introduced based on their distinct lineages and unique morphology.The new Dothideomycete genera Pseudomassariosphaeria(Amniculicolaceae),Heracleicola,Neodidymella and Pseudomicrosphaeriopsis(Didymellaceae),Pseudopithomyces(Didymosphaeriaceae),Brunneoclavispora,Neolophiostoma and Sulcosporium(Halotthiaceae),Lophiohelichrysum(Lophiostomataceae),Galliicola,Populocrescentia and Vagicola(Phaeosphaeriaceae),Ascocylindrica(Ascocylindricaceae),Elongatopedicellata(Roussoellaceae),Pseudoasteromassaria(Latoruaceae)and Pseudomonodictys(Macrodiplodiopsidaceae)are introduced.The newly described species of Dothideomycetes(Ascomycota)are Pseudomassariosphaeria bromicola(Amniculicolaceae),Flammeascoma lignicola(Anteagloniaceae),Ascocylindrica marina(Ascocylindricaceae),Lembosia xyliae(Asterinaceae),Diplodia crataegicola and Diplodia galiicola(Botryosphaeriaceae),Caryospora aquatica(Caryosporaceae),Heracleicola premilcurensis and Neodidymella thailandicum(Didymellaceae),Pseudopithomyces palmicola(Didymosphaeriaceae),Floricola viticola(Floricolaceae),Brunneoclavispora bambusae,Neolophiostoma pigmentatum and Sulcosporium thailandica(Halotthiaceae),Pseudoasteromassaria fagi(Latoruaceae),Keissleriella dactylidicola(Lentitheciaceae),Lophiohelichrysum helichrysi(Lophiostomataceae),Aquasubmersa japonica(Lophiotremataceae),Pseudomonodictys tectonae(Macrodiplodiopsidaceae),Microthyrium buxicola and Tumidispora shoreae(Microthyriaceae),Alloleptosphaeria clematidis,Allophaeosphaeria cytisi,Allophaeosphaeria subcylindrospora,Dematiopleospora luzulae,Entodesmium artemisiae,Galiicola pseudophaeosphaeria,Loratospora luzulae,Nodulosphaeria senecionis,Ophiosphaerella aquaticus,Populocrescentia forlicesenensis and Vagicola vagans(Phaeosphaeriaceae),Elongatopedicellata lignicola,Roussoella magnatum an
基金Supported by University of Manitoba Start-up funds and an award from the Manitoba Medical Service Foundation to Ghavami SUniversity of Manitoba Start-up Funds to Alizadeh J
文摘AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response(UPR) in hepatitis B(HBV) and C(HCV) infected hepatocytes.METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP(GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. AntiHCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy(LC3β punctuate), apoptosis(cleaved caspase-3), and unfolded protein response(GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows(Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent noninfected cells.RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase(P < 0.001) in apoptosis(cleavage of caspase-3), autophagy(LC3β punctate), and UPR(increase in GRP78 expression) in the HCV- and HBVinfected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBV^(Neg) and HBV^(Pos) revealed that majority of HBVinfected hepatocytes display strong positive stainingfor LC3β. Interestingly, although XBP splicing in HBVinfected cells was significantly higher(P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells(P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR.CONCLUSION: The results of this stu
基金the National Natural Science Foundation of China(No.30770013,No.31500013,No.31000013,No.31360014,No.31470152)the Special Program of Basic Science of the Ministry of Science and Technology(No.2012FY111600)the Technology of and International Cooperation Program of the Ministry of Science and Technology(No.2009DFA31160)of the People’s Republic of China,and the opening funding of State key Laboratory of Mycology,Institute of Microbiology,Chinese Academy of Sciences for funding。
文摘Notes on 113 fungal taxa are compiled in this paper,including 11 new genera,89 new species,one new subspecies,three new combinations and seven reference specimens.Awide geographic and taxonomic range of fungal taxa are detailed.In the Ascomycota the new genera Angustospora(Testudinaceae),Camporesia(Xylariaceae),Clematidis,Crassiparies(Pleosporales genera incertae sedis),Farasanispora,Longiostiolum(Pleosporales genera incertae sedis),Multilocularia(Parabambusicolaceae),Neophaeocryptopus(Dothideaceae),Parameliola(Pleosporales genera incertae sedis),and Towyspora(Lentitheciaceae)are introduced.Newly introduced species are Angustospora nilensis,Aniptodera aquibella,Annulohypoxylon albidiscum,Astrocystis thailandica,Camporesia sambuci,Clematidis italica,Colletotrichum menispermi,C.quinquefoliae,Comoclathris pimpinellae,Crassiparies quadrisporus,Cytospora salicicola,Diatrype thailandica,Dothiorella rhamni,Durotheca macrostroma,Farasanispora avicenniae,Halorosellinia rhizophorae,Humicola koreana,Hypoxylon lilloi,Kirschsteiniothelia tectonae,Lindgomyces okinawaensis,Longiostiolum tectonae,Lophiostoma pseudoarmatisporum,Moelleriella phukhiaoensis,M.pongdueatensis,Mucoharknessia anthoxanthi,Multilocularia bambusae,Multiseptospora thysanolaenae,Neophaeocryptopus cytisi,Ocellularia arachchigei,O.ratnapurensis,Ochronectria thailandica,Ophiocordyceps karstii,Parameliola acaciae,P.dimocarpi,Parastagonospora cumpignensis,Pseudodidymosphaeria phlei,Polyplosphaeria thailandica,Pseudolachnella brevifusiformis,Psiloglonium macrosporum,Rhabdodiscus albodenticulatus,Rosellinia chiangmaiensis,Saccothecium rubi,Seimatosporium pseudocornii,S.pseudorosae,Sigarispora ononidis and Towyspora aestuari.New combinations are provided for Eutiarosporella dactylidis(sexual morph described and illus trated)and Pseudocamarosporium pini.Descriptions,illustrations and/or reference specimens are designated for Aposphaeria corallinolutea,Cryptovalsa ampelina,Dothiorella vidmadera,Ophiocordyceps formosana,Petrakia echinata,Phragmoporthe conformis and Pse
基金MIUR grants PRIN, No.2003060498_002 and No. 2005067975_002 to Dr. Alvaro and by a grant award from Scott & White Hospital and The Texas A&M University System Health Science Center, a VA Merit Award, a VA Research Scholar Award and the NIH grants DK58411 and DK062975 to Dr. Alpini
文摘The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors （ER-α） and （ER-β） subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades JERK1/2 （extracellular regulated kinases 1/2, PI3-kinase/AKT （phosphatidylinositol-3＇ kinase/AKT）] typical of growth factors such as insulin like growth factor （IGF1）, nerve growth factor （NGF） and vascular endothelial growth factor （VEGF）, thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.
基金supported by the National Natural Science Foundation of China(81230002,81300057,91019016,31361163004)National Basic Research Program of China(2012CB316503)+3 种基金Ministry of Health(201302017)Ministry of Science and Technology of China(2006AA02Z152)Program of Introducing Talents of Discipline to Universities(B08007)the support of the Science and Technology Commission of Shanghai Municipality(07pj14096)
文摘Ebola virus （EBOV） causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein （GP） mediates widespread inflammation and cellular damage, these changes have mainly focused on alterations at the protein level, the role of microRNAs （miRNAs） in the molecular pathogenesis underlying this lethal disease is not fully understood. Here, we report that the miRNAs hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells （HUVECs） following expression of EBOV GP. Among the proteins encoded by predicted targets of these miRNAs, the adhesion-related molecules tissue factor pathway inhibitor （TFPI）, dystroglycan! （DAG1） and the caspase 8 and FADD-like apoptosis regulator （CFLAR） were significantly downregulated in EBOV GP-expressing HUVECs. Moreover, inhibition of hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p, or overexpression of TFPI, DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP. Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.
基金Wen are grateful to The National Natural Science Foundation of China(No.31460012,No.31200016).
文摘Taxonomic names are key links between various databases that store information on different organisms.Several global fungal nomenclural and taxonomic databases(notably Index Fungorum,Species Fungorum and MycoBank)can be sourced to find taxonomic details about fungi,while DNA sequence data can be sourced from NCBI,EBI and UNITE databases.Although the sequence data may be linked to a name,the quality of the metadata is variable and generally there is no corresponding link to images,descriptions or herbarium material.There is generally no way to establish the accuracy of the names in these genomic databases,other than whether the submission is from a reputable source.To tackle this problem,a new database(FacesofFungi),accessible at www.facesoffungi.org(FoF)has been established.This fungal database allows deposition of taxonomic data,phenotypic details and other useful data,which will enhance our current taxonomic understanding and ultimately enable mycologists to gain better and updated insights into the current fungal classification system.In addition,the database will also allow access to comprehensive metadata including descriptions of voucher and type specimens.This database is user-friendly,providing links and easy access between taxonomic ranks,with the classification system based primarily on molecular data(from the literature and via updated web-based phylogenetic trees),and to a lesser extent on morphological data when molecular data are unavailable.In FoF species are not only linked to the closest phylogenetic representatives,but also relevant data is provided,wherever available,on various applied aspects,such as ecological,industrial,quarantine and chemical uses.The data include the three main fungal groups(Ascomycota,Basidiomycota,Basal fungi)and fungus-like organisms.The FoF webpage is an output funded by the Mushroom Research Foundation which is an NGO with seven directors with mycological expertise.The webpage has 76 curators,and with the help of these specialists,FoF will provide an updated natural c
基金This work was supported by the Young Clinical Scientist Award from the Flight Attendant Medical Research Institute(FAMRI-123253_YCSA_Faculty)
文摘Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologies due to excessive inflammation.Professional phagocytes such as neutrophils(PMNs),eosinophils,monocytes,and macrophages use superoxide-generating NADPH oxidase(NOX)as part of their arsenal of antimicrobial mechanisms to produce high levels of ROS.NOX is a multisubunit enzyme complex composed of five essential subunits,two of which are localized in the membrane,while three are localized in the cytosol.In resting phagocytes,the oxidase complex is unassembled and inactive;however,it becomes activated after cytosolic components translocate to the membrane and are assembled into a functional oxidase.The NOX isoforms play a variety of roles in cellular differentiation,development,proliferation,apoptosis,cytoskeletal control,migration,and contraction.Recent studies have identified NOX as a major contributor to disease pathologies,resulting in a shift in focus on inhibiting the formation of potentially harmful free radicals.Therefore,a better understanding of the molecular mechanisms and the transduction pathways involved in NOX-mediated signaling is essential for the development of new therapeutic agents that minimize the hyperproduction of ROS.The current review provides a thorough overview of the various NOX enzymes and their roles in disease pathophysiology,highlights pharmacological strategies,and discusses the importance of computational modeling for future NOX-related studies.
文摘Nonalcoholic fatty liver disease （NAFLD）, an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.
基金Saowaluck Tibpromma would like to thank the Molecular Biology Experimental Center at Kunming Institute of Botany for facilities for molecular work,the Mushroom Research Foundation(MRF)Chiang Rai,Thailand for the financial support of her study and Shaun Pennycook is thanked for nomenclatural advice.K.D.Hyde would like to thank the Thailand Research Fund Grant No.RSA5980068 entitled“Biodiversity,phylogeny and role of fungal endophytes on above parts of Rhizophora apiculata and Nypa fruticans”+6 种基金the Chinese Academy of Sciences,Project Number 2013T2S0030for the award of Visiting Professorship for Senior International Scientists at Kunming Institute of Botany and National Research Council of Thailand(Mae Fah Luang University)for a grants“Biodiversity,phylogeny and role of fungal endophytes of Pandanaceae”(Grant No.:592010200112)“Diseases of mangrove trees and maintenance of good forestry practice”(Grant No.:60201000201)for supporting this study.S.C.Karunarathna,P.E.Mortimer and J.C.Xu would like to thank the World Agroforestry Centre,East and Central Asia OfficeKey Laboratory for Plant Diversity and Biogeography of East Asia,Kunming Institute of Botany,Chinese Academy of Sciencethe ChineseMinistry of Science and Technology,under the 12th 5-year National Key Technology Support Program(NKTSP)2013 BAB07B06 integration and comprehensive demonstration of key technologies on Green Phosphate-mountaion Construction and the CGIAR Research Program 6:Forest,Trees and Agroforestry for partial funding.The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research group NO(RG-1436-025)Financial support by the German Academic Exchange Service(DAAD)and the Thai Royal Golden Ph.D.Jubilee-Industry program(RGJ)for a joint TRFDAAD PPP(2012-2014)academic exchange grant to K.D.Hyde and M.Stadler,and the RGJ for a personal grant to B.Thongbai(No.Ph.D/0138/2553 in 4.S.MF/53/A.3)is gratefully acknowledged.Chayanard Phukhamsakda(PHD/0020/25
文摘This is a continuity of a series of taxonomic and phylogenetic papers on the fungi where materials were collected from many countries,examined and described.In addition to extensive morphological descriptions and appropriate asexual and sexual connections,DNA sequence data are also analysed from concatenated datasets to infer phylogenetic relationships and substantiate systematic positions of taxa within appropriate ranks.Wherever new species or combinations are proposed,we apply an integrative approach using morphological and molecular data as well as ecological features wherever applicable.Notes on 112 fungal taxa are compiled in this paper including Biatriosporaceae and Roussoellaceae,Didysimulans gen.nov.,81 new species,18 new host records and new country records,five reference specimens,two new combinations,and three sexual and asexual morph reports.The new species are Amanita cornelii,A.emodotrygon,Angustimassarina alni,A.arezzoensis,A.italica,A.lonicerae,A.premilcurensis,Ascochyta italica,A.rosae,Austroboletus appendiculatus,Barriopsis thailandica,Berkleasmium ariense,Calophoma petasitis,Camarosporium laburnicola,C.moricola,C.grisea,C.ossea,C.paraincrustata,Colletotrichum sambucicola,Coprinopsis cerkezii,Cytospora gelida,Dacrymyces chiangraiensis,Didysimulans italica,D.mezzanensis,Entodesmium italica,Entoloma magnum,Evlachovaea indica,Exophiala italica,Favolus gracilisporus,Femsjonia monospora,Fomitopsis flabellata,F.roseoalba,Gongronella brasiliensis,Helvella crispoides,Hermatomyces chiangmaiensis,H.chromolaenae,Hysterium centramurum,Inflatispora caryotae,Inocybe brunneosquamulosa,I.luteobrunnea,I.rubrobrunnea,Keissleriella cirsii,Lepiota cylindrocystidia,L.flavocarpa,L.maerimensis,Lophiotrema guttulata,Marasmius luculentus,Morenoina calamicola,Moelleriella thanathonensis,Mucor stercorarius,Myrmecridium fluviae,Myrothecium septentrionale,Neosetophoma garethjonesii,Nigrograna cangshanensis,Nodulosphaeria guttulatum,N.multiseptata,N.sambuci,Panus subfasciatus,Paraleptosphaeria padi,Paraphaeosphaeri
文摘Realizing personalized medicine requires integrating diverse data types with bioinformatics.The most vital data are genomic information for individuals that are from advanced next-generation sequencing(NGS) technologies at present.The technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the data.The prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work alike.Bioinformatics is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized medicine.We review some key bioinformatics tasks,issues,and challenges in contexts of IT requirements,data quality,analysis tools and pipelines,and validation of biomarkers.
基金funding support from the National Natural Science Foundation of China(Grant Nos.81672467,81702773,81702389,and 81672368)the Major National R&D Project(Grant Nos.2018ZX10723204,2018ZX10302205,and 2018ZX09J18107)the Natural Science Foundation of Beijing(Grant No.7172207)。
文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.
文摘Cancer stem cell （CSC） theory suggests a cell-lineage structure in tumor cells in which CSCs are capable of giving rise to the other non-stem cancer cells （NSCCs） but not vice versa. However, an alternative scenario of bidirectional interconversions between CSCs and NSCCs was proposed very recently. Here we present a general population model of cancer cells by integrating conventional cell divisions with direct conversions between different cell states, namely, not only can CSCs differentiate into NSCCs by asymmetric cell division, NSCCs can also dedifferentiate into CSCs by cell state conversion. Our theoretical model is validated when applying the model to recent experimental data. It is also found that the transient increase in CSCs proportion initiated from the purified NSCCs subpopulation cannot be well predicted by the conventional CSC model where the conversion from NSCCs to CSCs is forbidden, implying that the cell state conversion is required especially for the transient dynamics. The theoretical analysis also gives the condition such that our general model can be equivalently reduced into a simple Markov chain with only cell state transitions keeping the same cell proportion dynamics.
基金supported by the National Natural Science Foundation of China (Grant Nos.61370035 and 31361163004)Tsinghua University Initiative Scientific Research Program
文摘Single-cell RNA sequencing(scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell subpopulations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data(VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.
基金supported by NYUAD Faculty Research Funds(AD060)Tamkeen under the NYU Abu Dhabi Research Institute Award to the NYUAD Center for Genomics and Systems Biology(7371210 CGSB9)。
文摘Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.
基金supported by grants from Regione Campania (L.R. N.5 Bando 2003 to MP)the Italian Minister of Research and University (PRIN 2007 to MP,PRIN 2017-2017XJ38A4_003 to GC and MP)UNIMIB (Progetto ID 2019-ATESP-0001 and Progetto ID 2018-CONV-0056 to AV)。
文摘Decades of research in glial biology have investigated mechanisms of neuro-glial interplay,demonstrating that neurons and glia intimately cooperate for energy metabolism in the central nervous system(CNS)(Magistretti and Allaman,2018).
基金Supported by the Faculty of Medicine,Ramathibodi Hospital,Mahidol University。
文摘BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.
