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1.
Nature ; 628(8009): 771-775, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38632399

RESUMO

Quantitative detection of various molecules at very low concentrations in complex mixtures has been the main objective in many fields of science and engineering, from the detection of cancer-causing mutagens and early disease markers to environmental pollutants and bioterror agents1-5. Moreover, technologies that can detect these analytes without external labels or modifications are extremely valuable and often preferred6. In this regard, surface-enhanced Raman spectroscopy can detect molecular species in complex mixtures on the basis only of their intrinsic and unique vibrational signatures7. However, the development of surface-enhanced Raman spectroscopy for this purpose has been challenging so far because of uncontrollable signal heterogeneity and poor reproducibility at low analyte concentrations8. Here, as a proof of concept, we show that, using digital (nano)colloid-enhanced Raman spectroscopy, reproducible quantification of a broad range of target molecules at very low concentrations can be routinely achieved with single-molecule counting, limited only by the Poisson noise of the measurement process. As metallic colloidal nanoparticles that enhance these vibrational signatures, including hydroxylamine-reduced-silver colloids, can be fabricated at large scale under routine conditions, we anticipate that digital (nano)colloid-enhanced Raman spectroscopy will become the technology of choice for the reliable and ultrasensitive detection of various analytes, including those of great importance for human health.


Assuntos
Coloides , Imagem Individual de Molécula , Análise Espectral Raman , Coloides/química , Hidroxilamina/química , Nanopartículas Metálicas/química , Distribuição de Poisson , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Prata/química , Imagem Individual de Molécula/métodos , Imagem Individual de Molécula/normas , Análise Espectral Raman/métodos , Análise Espectral Raman/normas , Vibração
2.
Immunity ; 49(5): 915-928.e5, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30446384

RESUMO

Innate lymphoid cells (ILCs) are important for mucosal immunity. The intestine harbors all ILC subsets, but how these cells are balanced to achieve immune homeostasis and mount appropriate responses during infection remains elusive. Here, we show that aryl hydrocarbon receptor (Ahr) expression in the gut regulates ILC balance. Among ILCs, Ahr is most highly expressed by gut ILC2s and controls chromatin accessibility at the Ahr locus via positive feedback. Ahr signaling suppresses Gfi1 transcription-factor-mediated expression of the interleukin-33 (IL-33) receptor ST2 in ILC2s and expression of ILC2 effector molecules IL-5, IL-13, and amphiregulin in a cell-intrinsic manner. Ablation of Ahr enhances anti-helminth immunity in the gut, whereas genetic or pharmacological activation of Ahr suppresses ILC2 function but enhances ILC3 maintenance to protect the host from Citrobacter rodentium infection. Thus, the host regulates the gut ILC2-ILC3 balance by engaging the Ahr pathway to mount appropriate immunity against various pathogens.


Assuntos
Imunidade Inata , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Biomarcadores , Cromatina/genética , Cromatina/metabolismo , Citrobacter rodentium/imunologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Loci Gênicos , Interações Hospedeiro-Parasita/imunologia , Imunidade nas Mucosas/genética , Imunofenotipagem , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Knockout , Receptores de Hidrocarboneto Arílico/genética , Transcriptoma
3.
J Immunol ; 213(5): 730-742, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38984862

RESUMO

Teleost IgM+ B cells can phagocytose, like mammalian B1 cells, and secrete Ag-specific IgM, like mammalian B2 cells. Therefore, teleost IgM+ B cells may have the functions of both mammalian B1 and B2 cells. To support this view, we initially found that grass carp (Ctenopharyngodon idella) IgM+ plasma cells (PCs) exhibit robust phagocytic ability, akin to IgM+ naive B cells. Subsequently, we sorted grass carp IgM+ PCs into two subpopulations: nonphagocytic (Pha-IgM+ PCs) and phagocytic IgM+ PCs (Pha+IgM+ PCs), both of which demonstrated the capacity to secrete natural IgM with LPS and peptidoglycan binding capacity. Remarkably, following immunization of grass carp with an Ag, we observed that both Pha-IgM+ PCs and Pha+IgM+ PCs could secrete Ag-specific IgM. Furthermore, in vitro concatenated phagocytosis experiments in which Pha-IgM+ PCs from an initial phagocytosis experiment were sorted and exposed again to beads confirmed that these cells also have phagocytic capabilities, thereby suggesting that all teleost IgM+ B cells have phagocytic potential. Additionally, we found that grass carp IgM+ PCs display classical phenotypic features of macrophages, providing support for the hypothesis that vertebrate B cells evolved from ancient phagocytes. These findings together reveal that teleost B cells are a primitive B cell type with functions reminiscent of both mammalian B1 and B2 cells, providing insights into the origin and evolution of B cells in vertebrates.


Assuntos
Linfócitos B , Carpas , Imunoglobulina M , Fagocitose , Plasmócitos , Animais , Carpas/imunologia , Imunoglobulina M/imunologia , Fagocitose/imunologia , Plasmócitos/imunologia , Linfócitos B/imunologia , Fagócitos/imunologia , Evolução Biológica
4.
Acc Chem Res ; 57(18): 2728-2745, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39226463

RESUMO

ConspectusCarbon dioxide (CO2) is recognized as a greenhouse gas and a common waste product. Simultaneously, it serves as an advantageous and commercially available C1 building block to generate valuable chemicals. Particularly, carboxylation with CO2 is considered a significant method for the direct and sustainable production of important carboxylic acids. However, the utilization of CO2 is challenging owing to its thermodynamic stability and kinetic inertness. Recently, organic electrosynthesis has emerged as a promising approach that utilizes electrons or holes as environmentally friendly redox reagents to produce reactive intermediates in a controlled and selective manner. This technique holds great potential for the CO2 utilization.Since 2015, our group has been dedicated to exploring the utilization of CO2 in organic synthesis with a particular focus on electrochemical carboxylation. Despite the significant advancements made in this area, there are still many challenges, including the activation of inert substrates, regulation of selectivity, diversity in electrolysis modes, and activation strategies. Over the past 7 years, our team, with many great experts, has presented findings on electrochemical carboxylation with CO2 under mild conditions. In this context, we primarily highlight our contributions to selective electrocarboxylations, encompassing new reaction systems, selectivity control methods, and activation approaches.We commenced our research by establishing a Ni-catalyzed electrochemical carboxylation of unactivated aryl halides and alkyl bromides in conjunction with a useful paired anodic reaction. This approach eliminates the need for sacrificial anodes, rendering the carboxylation process sustainable. To further utilize the widely existing yet cost-effective alkyl chlorides, we have developed a deep electroreductive system to achieve carboxylation of unactivated alkyl chlorides and poly(vinyl chloride), allowing the direct modification and upgrading of waste polymers.Through precise adjustment of the electroreductive conditions, we successfully demonstrated the dicarboxylation of both strained carbocycles and acyclic polyarylethanes with CO2 via C-C bond cleavage. Furthermore, we have realized the dicarboxylative cyclization of unactivated skipped dienes to produce the valuable ring-tethered adipic acids through single-electron reduction of CO2 to the CO2 radical anion (CO2•-). In terms of the asymmetric carboxylation, Guo's and our groups have recently achieved the nickel-catalyzed enantioselective electroreductive carboxylation reaction using racemic propargylic carbonates and CO2, paving the way for the synthesis of enantioenriched propargylic carboxylic acids.In addition to the aforementioned advancements, Lin's and our groups have also developed new electrolysis modes to achieve regiodivergent C-H carboxylation of N-heteroarenes dictated by electrochemical reactors. The choice of reactors plays a crucial role in determining whether the hydrogen atom transfer (HAT) reagents are formed anodically, consequently influencing the carboxylation pathways of N-heteroarene radical anions in the distinct electrolyzed environments.

5.
Nucleic Acids Res ; 51(D1): D29-D38, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36370100

RESUMO

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. New resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, IgBLAST, GDV, RefSeq, NCBI Virus, GenBank type assemblies, iCn3D, ClinVar, GTR, dbGaP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.


Assuntos
Bases de Dados Genéticas , Bases de Dados de Ácidos Nucleicos , Estados Unidos , National Library of Medicine (U.S.) , Alinhamento de Sequência , Biotecnologia , Internet
6.
BMC Biol ; 22(1): 179, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39183278

RESUMO

BACKGROUND: Cell wall integrity (CWI) is crucial for fungal growth, pathogenesis, and adaptation to extracellular environments. Calcofluor white (CFW) is a cell wall perturbant that inhibits fungal growth, yet little is known about how phytopathogenic fungi respond to the CFW-induced stress. RESULTS: In this study, we unveiled a significant discovery that CFW triggered the translocation of the transcription factor CgCrzA from the cytoplasm to the nucleus in Colletotrichum gloeosporioides. This translocation was regulated by an interacting protein, CgMkk1, a mitogen-activated protein kinase involved in the CWI pathway. Further analysis revealed that CgMkk1 facilitated nuclear translocation by phosphorylating CgCrzA at the Ser280 residue. Using chromatin immunoprecipitation sequencing, we identified two downstream targets of CgCrzA, namely CgCHS5 and CgCHS6, which are critical for growth, cell wall integrity, and pathogenicity as chitin synthase genes. CONCLUSIONS: These findings provide a novel insight into the regulatory mechanism of CgMkk1-CgCrzA-CgChs5/6, which enables response of the cell wall inhibitor CFW and facilitates infectious growth for C. gloeosporioides.


Assuntos
Colletotrichum , Proteínas Fúngicas , Fatores de Transcrição , Virulência/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Colletotrichum/genética , Colletotrichum/patogenicidade , Parede Celular/metabolismo , Regulação Fúngica da Expressão Gênica , Fosforilação
7.
J Neurosci ; 43(11): 1859-1870, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36725322

RESUMO

Age-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available up-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13-18 months) and old (20-22 months) mice of either sex compared with adult mice (3-8 months), accompanied by functional deficits. Oligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL turnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis displayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and visual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice. Genetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual function. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clemastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine treatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved visual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and visual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function.SIGNIFICANCE STATEMENT Oligodendrocyte (OL) turnover has been reported in adult optic nerves (ONs), but the longitudinal change and functional significance of OL turnover during aging remain largely unknown. Using cell-lineage tracing and oligodendroglia-specific manipulation, this study reported that OL generation was active in adult ONs and the efficiency decreased in an age-dependent manner. Genetically dampening OL generation by Olig2 ablation resulted in significant axon loss and retinal degeneration, along with delayed visual signal transmission. Conversely, pro-myelination approaches significantly increased new myelin generation in aging ONs, and consequently preserved retinal integrity and visual function. Our findings indicate that promoting OL generation might be a promising strategy to preserve visual function from age-related decline.


Assuntos
Clemastina , Degeneração Retiniana , Camundongos , Animais , Clemastina/farmacologia , Oligodendroglia/fisiologia , Bainha de Mielina/fisiologia , Nervo Óptico , Axônios , Diferenciação Celular/fisiologia
8.
Glia ; 72(9): 1555-1571, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38829008

RESUMO

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.


Assuntos
Clemastina , Glaucoma , Camundongos Endogâmicos C57BL , Remielinização , Retina , Animais , Clemastina/farmacologia , Clemastina/uso terapêutico , Glaucoma/patologia , Glaucoma/tratamento farmacológico , Retina/patologia , Retina/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Remielinização/fisiologia , Camundongos , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Modelos Animais de Doenças , Doenças do Nervo Óptico/tratamento farmacológico , Doenças do Nervo Óptico/patologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia
9.
J Am Chem Soc ; 146(5): 2919-2927, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38277794

RESUMO

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

10.
Small ; : e2402235, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845530

RESUMO

The field of second near-infrared (NIR-II) surface-enhanced Raman scattering (SERS) nanoprobes has made commendable progress in biomedicine. This article reviews recent advances and future development of NIR-II SERS nanoprobes. It introduces the fundamental principles of SERS nanoprobes and highlights key advances in the NIR-II window, including reduced tissue attenuation, deep penetration, maximized allowable exposure, and improved photostability. The discussion of future directions includes the refinement of nanoprobe substrates, emphasizing the tailoring of optical properties of metallic SERS-active nanoprobes, and exploring non-metallic alternatives. The intricacies of designing Raman reporters for the NIR-II resonance and the potential of these reporters to advance the field are also discussed. The integration of artificial intelligence (AI) into nanoprobe design represents a cutting-edge approach to overcome current challenges. This article also examines the emergence of deep Raman techniques for through-tissue SERS detection, toward NIR-II SERS tomography. It acknowledges instrumental advancements like improved charge-coupled device sensitivity and accelerated imaging speeds. The article concludes by addressing the critical aspects of biosafety, ease of functionalization, compatibility, and the path to clinical translation. With a comprehensive overview of current achievements and future prospects, this review aims to illuminate the path for NIR-II SERS nanoprobes to innovate diagnostic and therapeutic approaches in biomedicine.

11.
Proc Biol Sci ; 291(2031): 20240642, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39288804

RESUMO

Nutrient addition, particularly nitrogen, often increases plant aboveground biomass but causes species loss. Asymmetric competition for light is frequently assumed to explain the biomass-driven species loss. However, it remains unclear whether other factors such as water can also play a role. Increased aboveground leaf area following nitrogen addition and warming may increase transpiration and cause water limitation, leading to a decline in diversity. To test this, we conducted field measurements in a grassland community exposed to nitrogen and water addition, and warming. We found that warming and/or nitrogen addition significantly increased aboveground biomass but reduced species richness. Water addition prevented species loss in either nitrogen-enriched or warmed treatments, while it partially mitigated species loss in the treatment exposed to increases in both temperature and nitrogen. These findings thus strongly suggest that water limitation can be an important driver of species loss as biomass increases after nitrogen addition and warming when soil moisture is limiting. This result is further supported by a meta-analysis of published studies across grasslands worldwide. Our study indicates that loss of grassland species richness in the future may be greatest under a scenario of increasing temperature and nitrogen deposition, but decreasing precipitation.


Assuntos
Biodiversidade , Biomassa , Pradaria , Nitrogênio , Água , Nitrogênio/metabolismo , Temperatura , Aquecimento Global , Poaceae/fisiologia
12.
Metab Eng ; 81: 227-237, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072357

RESUMO

5-Aminovaleric acid (5-AVA), 5-hydroxyvalerate (5HV), copolymer P(3HB-co-5HV) of 3-hydroxybutyrate (3HB) and 5HV were produced from L-lysine as a substrate by recombinant Halomonas bluephagenesis constructed based on codon optimization, deletions of competitive pathway and L-lysine export protein, and three copies of davBA genes encoding L-lysine monooxygenase (DavB) and 5-aminovaleramide amidohydrolase (DavA) inserted into its genome to form H. bluephagenesis YF117ΔgabT1+2, which produced 16.4 g L-1 and 67.4 g L-1 5-AVA in flask cultures and in 7 L bioreactor, respectively. It was able to de novo synthesize 5-AVA from glucose by L-lysine-overproducing H. bluephagenesis TD226. Corn steep liquor was used instead of yeast extract for cost reduction during the 5-AVA production. Using promoter engineering based on Pporin mutant library for downstream genes, H. bluephagenesis YF117 harboring pSEVA341-Pporin42-yqhDEC produced 6 g L-1 5HV in shake flask growth, while H. bluephagenesis YF117 harboring pSEVA341-Pporin42-yqhDEC-Pporin278-phaCRE-abfT synthesized 42 wt% P(3HB-co-4.8 mol% 5HV) under the same condition. Thus, H. bluephagenesis was successfully engineered to produce 5-AVA and 5HV in supernatant and intracellular P(3HB-co-5HV) utilizing L-lysine as the substrate.


Assuntos
Halomonas , Engenharia Metabólica , Lisina/genética , Lisina/metabolismo , Halomonas/genética , Halomonas/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Poliésteres/metabolismo , Porinas/genética , Porinas/metabolismo
13.
Metab Eng ; 81: 249-261, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38159902

RESUMO

Predictability and robustness are challenges for bioproduction because of the unstable intracellular synthetic activities. With the deeper understanding of the gene expression process, fine-tuning has become a meaningful tool for biosynthesis optimization. This study characterized several gene expression elements and constructed a multiple inducible system that responds to ten different small chemical inducers in halophile bacterium Halomonas bluephagenesis. Genome insertion of regulators was conducted for the purpose of gene cluster stabilization and regulatory plasmid simplification. Additionally, dynamic ranges of the multiple inducible systems were tuned by promoter sequence mutations to achieve diverse scopes for high-resolution gene expression control. The multiple inducible system was successfully employed to precisely control chromoprotein expression, lycopene and poly-3-hydroxybutyrate (PHB) biosynthesis, resulting in colorful bacterial pictures, optimized cell growth, lycopene and PHB accumulation. This study demonstrates a desirable approach for fine-tuning of rational and efficient gene expressions, displaying the significance for metabolic pathway optimization.


Assuntos
Halomonas , Poliésteres , Poliésteres/metabolismo , Halomonas/genética , Halomonas/metabolismo , Licopeno/metabolismo , Biotecnologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Engenharia Metabólica/métodos
14.
Metab Eng ; 84: 95-108, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38901556

RESUMO

Microbial instability is a common problem during bio-production based on microbial hosts. Halomonas bluephagenesis has been developed as a chassis for next generation industrial biotechnology (NGIB) under open and unsterile conditions. However, the hidden genomic information and peculiar metabolism have significantly hampered its deep exploitation for cell-factory engineering. Based on the freshly completed genome sequence of H. bluephagenesis TD01, which reveals 1889 biological process-associated genes grouped into 84 GO-slim terms. An enzyme constrained genome-scale metabolic model Halo-ecGEM was constructed, which showed strong ability to simulate fed-batch fermentations. A visible salt-stress responsive landscape was achieved by combining GO-slim term enrichment and CVT-based omics profiling, demonstrating that cells deploy most of the protein resources by force to support the essential activity of translation and protein metabolism when exposed to salt stress. Under the guidance of Halo-ecGEM, eight transposases were deleted, leading to a significantly enhanced stability for its growth and bioproduction of various polyhydroxyalkanoates (PHA) including 3-hydroxybutyrate (3HB) homopolymer PHB, 3HB and 3-hydroxyvalerate (3HV) copolymer PHBV, as well as 3HB and 4-hydroxyvalerate (4HB) copolymer P34HB. This study sheds new light on the metabolic characteristics and stress-response landscape of H. bluephagenesis, achieving for the first time to construct a long-term growth stable chassis for industrial applications. For the first time, it was demonstrated that genome encoded transposons are the reason for microbial instability during growth in flasks and fermentors.


Assuntos
Halomonas , Halomonas/genética , Halomonas/metabolismo , Halomonas/enzimologia , Halomonas/crescimento & desenvolvimento , Engenharia Metabólica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Redes e Vias Metabólicas/genética , Deleção de Genes , Modelos Biológicos
15.
Plant Cell Environ ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808618

RESUMO

Bursaphelenchus xylophilus is the pathogen of pine wilt disease, which can devastate the pine forest ecosystem. Usually, plant cells generate reactive oxygen species (ROS) as a defensive substance or signalling molecules to resist the infection of nematodes. However, little is known about how B. xylophilus effectors mediate the plant ROS metabolism. Here, we identified a pioneer B. xylophilus Prx3-interacting effector 1 (BxPIE1) expressed in the dorsal gland cells and the intestine. Silencing of the BxPIE1 gene resulted in reduced nematode reproduction and a delay in disease progression during parasitic stages, with the upregulation of pathogenesis-related (PR) genes PtPR-3 (class Ⅳ chitinase) and PtPR-9 (peroxidase). The protein-protein interaction assays further demonstrated that BxPIE1 interacts with a Pinus thunbergii class III peroxidase (PtPrx3), which produces H2O2 under biotic stress. The expression of BxPIE1 and PtPrx3 was upregulated during the infection stage. Furthermore, BxPIE1 effectively inhibited H2O2 generating from class III peroxidase and ascorbate can recover the virulence of siBxPIE1-treated B. xylophilus by scavenging H2O2. Taken together, BxPIE1 is an important virulence factor, revealing a novel mechanism utilized by nematodes to suppress plant immunity.

16.
Microvasc Res ; 151: 104611, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37774941

RESUMO

Pathological neovascularization is the hallmark of many vascular oculopathies. There is still a great deal of uncertainty surrounding retinal neovascularization research. A working hypothesis that astrocytic Yes-associated protein (YAP) act as a key factor in retinal neovascularization was proposed. And our study was conducted to verified this hypothesis. In vivo, we successfully generated mice deficient in YAP in astrocytes (YAPf/f GFAP-Cre mice) and set up oxygen-induced retinopathy (OIR) model. Pathological neovascularization was evaluated by immunofluorescence staining and western blotting. In vitro, cultured retinal astrocytes were transfected with YAP siRNA. Enzyme-linked immunosorbent assay (ELISA) and western blot were used to determine the proteins in the supernatants and cells. The results showed that YAP was upregulated and activated in the OIR mice retinas. Conditional ablation of YAP aggravated pathological neovascularization, along with the upregulation of vascular endothelial growth factor A (VEGF-A) and monocyte chemoattractant protein-1 (MCP-1). Studies in vitro confirmed that the knockdown of YAP in astrocytes lead to increases in VEGF-A and MCP-1 levels, thus enhancing pro-angiogenic capability of YAP-deficit astrocytes. In conclusion, astrocytic YAP alleviates retinal pathological angiogenesis by inhibiting the over-activation of astrocytes, which suppresses excessive VEGF-A production and neuroinflammation.


Assuntos
Neovascularização Retiniana , Animais , Camundongos , Neovascularização Retiniana/metabolismo , Oxigênio/toxicidade , Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neovascularização Patológica/metabolismo , Proteínas de Sinalização YAP , Astrócitos/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Animais Recém-Nascidos
17.
Microvasc Res ; 154: 104697, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38801942

RESUMO

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.


Assuntos
Neoplasias Cardíacas , Mixoma , Análise de Célula Única , Humanos , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/metabolismo , Mixoma/patologia , Mixoma/genética , Mixoma/cirurgia , Mixoma/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Células Epiteliais/patologia , Células Epiteliais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos T/patologia , Linfócitos T/metabolismo , Idoso , Adulto , Comunicação Celular , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Fenótipo
18.
Glob Chang Biol ; 30(7): e17430, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031432

RESUMO

The relationship between plant aboveground biomass and diversity typically follows a unimodal pattern, showing a positive correlation in resource-poor habitats and a negative correlation in resource-rich environments. Precipitation is a crucial resource for both plant biomass and diversity in terrestrial ecosystems. However, the impact of precipitation changes on the relationship between plant biomass and diversity remains unclear. We conduct a water addition field experiment in a semiarid grassland and identify a unimodal relationship between plant biomass and species richness under ambient conditions. Water addition delays the declining phase of this unimodal curve and shift it upward compared to ambient conditions. Our meta-analysis of water addition experiments conducted across major biomes worldwide (grassland, shrubland, desert, and forest) supports this finding, while water reduction does not alter the biomass-diversity relationship. Water addition increases biomass in all climate but only increases species richness in arid and semiarid climate. Similarly, water reduction decreases biomass in all climate but only reduces species richness in arid and semiarid climate. Species richness in dry subhumid and humid climate does not change significantly. Furthermore, our field experiment shows that water addition increases plant diversity while decreasing soil inorganic nitrogen levels. The increase in one resource, such as water, leads to the scarcity of another, such as nutrient, thus postponing the declining phase of the plant biomass-diversity relationship typically observed in resource-rich habitats. Our research contributes to predicting the plant biomass-diversity relationship under changing precipitation conditions and highlights the complex interplay between water availability, nutrient level, and plant diversity.


Assuntos
Biodiversidade , Biomassa , Água , Ecossistema , Pradaria , Nitrogênio/análise , Nitrogênio/metabolismo , Plantas , Chuva , Solo/química
19.
Sex Transm Dis ; 51(6): 400-406, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38403298

RESUMO

BACKGROUND: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among men who have sex with men (MSM) are escalating public health concerns. This study aimed to explore (1) the reliability of self-reported sexual positioning as an indicator for rectal CT and NG screening, and (2) factors associated with rectal CT and NG infections in Shenzhen, China. METHODS: A cross-sectional study was conducted in 2 settings in Shenzhen, China, from April 1, 2021, to March 31, 2022. Data on sociodemographic characteristics, sexual behaviors, and basic CT knowledge were collected. Urine and self-collected rectal swabs were collected for CT and NG testing. RESULTS: In total, 195 MSM participated in the study, and 5.1% tested positive for urogenital CT, 29.2% for rectal CT, 1.0% for urogenital NG, and 8.2% for rectal NG. Among those who reported exclusively insertive anal sex, 69.2% of CT infections and 85.7% of NG infections would have remained undetected with urine testing alone. Risk factors for rectal CT infection included engaging in both insertive and receptive anal sex, with a significant association found for coinfection with rectal NG. CONCLUSIONS: Self-reported sexual positioning was found to be an unreliable indicator for CT and NG screening, as a substantial proportion of infections would have remained undetected. The findings suggest that CT and NG screening in China should be offered to all MSM regardless of self-reported sexual positioning, and that the dual CT/NG testing is recommended.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Gonorreia , Homossexualidade Masculina , Neisseria gonorrhoeae , Autorrelato , Comportamento Sexual , Humanos , Masculino , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , China/epidemiologia , Estudos Transversais , Adulto , Neisseria gonorrhoeae/isolamento & purificação , Chlamydia trachomatis/isolamento & purificação , Programas de Rastreamento , Reto/microbiologia , Adulto Jovem , Fatores de Risco , Doenças Retais/microbiologia , Doenças Retais/diagnóstico , Doenças Retais/epidemiologia , Minorias Sexuais e de Gênero , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
20.
Hum Genomics ; 17(1): 29, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36973821

RESUMO

BACKGROUND: Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. RESULTS: Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. CONCLUSIONS: Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.


Assuntos
Cromossomos Humanos Y , População do Leste Asiático , Polimorfismo de Nucleotídeo Único , Humanos , China , Cromossomos Humanos Y/genética , População do Leste Asiático/genética , Genética Populacional , Haplótipos , Filogenia
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