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Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) is regarded as one of the most important priority pathogens within the One Health interface. However, few studies have investigated the occurrence of ESBL-EC in giant pandas, along with their antibiotic-resistant characteristics and horizontal gene transfer abilities. In this study, we successfully identified 12 ESBL-EC strains (8.33%, 12/144) out of 144 E. coli strains which isolated from giant pandas. We further detected antibiotic resistance genes (ARGs), virulence-associated genes (VAGs) and mobile genetic elements (MGEs) among the 12 ESBL-EC strains, and the results showed that 13 ARGs and 11 VAGs were detected, of which bla CTX-M (100.00%, 12/12, with 5 variants observed) and papA (83.33%, 10/12) were the most prevalent, respectively. And ISEcp1 (66.67%, 8/12) and IS26 (66.67%, 8/12) were the predominant MGEs. Furthermore, horizontal gene transfer ability analysis of the 12 ESBL-EC showed that all bla CTX-M genes could be transferred by conjugative plasmids, indicating high horizontal gene transfer ability. In addition, ARGs of rmtB and sul2, VAGs of papA, fimC and ompT, MGEs of ISEcp1 and IS26 were all found to be co-transferred with bla CTX-M. Phylogenetic analysis clustered these ESBL-EC strains into group B2 (75.00%, 9/12), D (16.67%, 2/12), and B1 (8.33%, 1/12), and 10 sequence types (STs) were identified among 12 ESBL-EC (including ST48, ST127, ST206, ST354, ST648, ST1706, and four new STs). Our present study showed that ESBL-EC strains from captive giant pandas are reservoirs of ARGs, VAGs and MGEs that can co-transfer with bla CTX-M via plasmids. Transmissible ESBL-EC strains with high diversity of resistance and virulence elements are a potential threat to humans, animals and surrounding environment.
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Vision plays a crucial role in the survival of animals, and the visual system has particularly selectively evolved in response to the visual environment, ecological niche, and species habitats in vertebrate species. To date, a horizontal streak of retinal ganglion cell (RGC) distribution pattern is observed across mammal species. Here, we report that the giant panda's vertically oriented visual streak, combined with current evidence of the animal's forward-placed eyes, ocular structure, and retinal neural topographic distribution patterns, presents the emergence of a well-adapted binocular visual system. Our results suggest that the giant panda may use a unique way to processing binocular visual information. Results of mathematical simulation are in favor of this hypothesis. The topographic distribution properties of RGCs reported here could be essential for understanding the visual adaptation and evolution of this living fossil.
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Células Ganglionares da Retina , Ursidae , Animais , Células Ganglionares da Retina/citologia , Ursidae/anatomia & histologia , Ursidae/fisiologia , Retina/citologia , Retina/anatomia & histologiaRESUMO
Transition metal-catalyzed enantioselective hydroamination of 1,3-dienes provides a direct methodology for the construction of chiral allylamines. So far, all of the reported examples used nucleophilic amines and proceeded with 3,4-regioselectivity. Herein, we describe the first example of nickel-catalyzed enantioselective 1,4-hydroamination of 1,3-dienes using trimethoxysilane and hydroxylamines with a structurally adaptable aromatic spiroketal based chiral diphosphine (SKP) as the ligand, affording a wide array of α-substituted chiral allylamines in high yields with excellent regio- and enantioselectivities. This operationally simple protocol demonstrated a broad substrate scope and excellent functional group compatibility, significantly expanding the chemical space for chiral allylamines. Experimental and DFT studies were performed to elucidate the mechanism and to rationalize the regio- and enantioselectivities of the reaction.
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Giant pandas have a high incidence of tooth wear, loss, and fracture since their diet is specifically bamboo. Dental implantation is a common treatment for tooth loss in humans while rarely reported in wild animals. To explore the applicability of dental implantation in giant pandas, this study measured mandible parameters of the giant panda, from an adult skeletal specimen. The mandible bone block model was developed using computer-aided design 3D mechanical drawing software. Implants of different radius and thread types of the third premolar tooth (PM3) were assembled and imported into an analysis software system for finite element analysis. As a result, the reverse buttress implant with a radius of 7.5â mm and 8.3â mm, and a length of 15â mm was found to be the most suitable implant for use in the giant panda PM3. This study provides a reference for appropriate clinical giant panda dental implantation, although, the feasibility of giant panda dental implantation needs to be studied further.
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Introduction: Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts. Methods: In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma. Results: We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side. Discussion: This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.
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Campylobacter , Fusobacterium , Microbiota , Boca , Porphyromonas , RNA Ribossômico 16S , Ursidae , Ursidae/microbiologia , Animais , RNA Ribossômico 16S/genética , Porphyromonas/genética , Porphyromonas/isolamento & purificação , Porphyromonas/classificação , Campylobacter/genética , Campylobacter/isolamento & purificação , Campylobacter/classificação , Boca/microbiologia , Fusobacterium/genética , Fusobacterium/isolamento & purificação , Fibroma/microbiologia , Fibroma/veterinária , Neisseria/isolamento & purificação , Neisseria/genética , Neisseria/classificação , Neoplasias Bucais/microbiologia , Neoplasias Bucais/veterinária , Neoplasias Bucais/patologia , Filogenia , Análise de Sequência de DNARESUMO
In this study, we have successfully constructed a comprehensive database of metagenome-assembled genomes (MAGs) pertaining to the gut microbiota of the giant panda. Through our analysis, we have identified significant reservoirs of antibiotic resistance genes (ARGs), namely Escherichia coli, Citrobacter portucalensis, and Klebsiella pneumoniae. Furthermore, we have elucidated the primary contributors to ARGs, including Streptococcus alactolyticus and Clostridium SGBP116, in both captive and wild pandas. Additionally, our findings have demonstrated a higher prevalence of ARGs in the metagenome, with notable expression of the RPOB2 gene in S. alactolyticus. Crucially, 1217 ARGs shared homology with human gut ARGs, underscoring the interaction relationship between pandas and human microbiomes. These findings are instrumental in understanding the antibiotic resistance landscape in the giant panda's gut, providing a framework for developing strategies to combat antibiotic resistance and safeguard the health of this endangered species.
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Escherichia coli (E. coli) plays an important ecological role, and is a useful bioindicator to recognize the evolution of resistance in human, animal and environment. Recently, extended-spectrum ß-lactamases (ESBL) producing E.coli has posed a threat to public health. Generally, captive healthy giant pandas are not exposed to antibiotics; however, they still acquire antimicrobial resistant bacteria. In order to understand whether there is an exchange of resistance genes within the ecosystems of captive giant pandas, this study explored resistance characteristics of 330 commensal E. coli isolates from feces of giant pandas, the surroundings, and breeders. Isolates from different sources showed similar resistance phenotype, and ESBL/AmpC-producing isolates showed more profound resistance to antibiotics than non-ESBL/AmpC-producing isolates (P<0.05). Furthermore, the occurrence of broad-spectrum ß-lactamase related resistance genes and colistin resistance genes was detected, and isolates phylogenetic typing and multilocus sequence typing (MLST) were applied in this study. Seven different ß-lactamase resistance genes (blaCTX-M-55, blaCTX-M-15, blaCTX-M-27, blaCTX-M-65, blaTEM-1, blaOXA-1 and blaCMY) and mcr-1 were found in 68 ESBL/AmpC-producing isolates. blaCTX-M-55 (48.53 %) was found the most predominant resistance genes, followed by blaTEM-1 (19.12 %) and blaCTX-M-27 (16.18 %). Nonetheless, blaCTX-M-55 was commonly detected in the isolates from giant pandas (63.16 %), the surroundings (43.48 %), and breeders (33.33 %). However, there were no carbapenemase genes detected in this study. mcr-1 was harbored in only one isolate from giant panda. Forty-five tansconjugants were successfully obtained in the conjugation experiments. The presence of antimicrobial resistance and related resistance genes tested were observed in the transconjugants. The results indicated that 52.63 % of the isolates from giant panda 73.91 % of the isolates from surroundings, and 100 % of the isolates from breeders were phylogroup A. Total of 27 sequence types (ST) were recognized from the isolate by MLST and found that ST48 (19/68; 27.94 %) was the predominant ST type, especially in the isolates from giant pandas and the surroundings. In conclusion, commensal ESBL/AmpC-producing E. coli becomes a reservoir of ESBL resistance genes, which is a potential threaten to health of giant pandas. The interaction between giant pandas, surroundings and breeders contribute to development of resistant phenotypes and genotypes which might transfer across species or the surroundings easily; hence, strict monitoring based on a "One Health" approach is recommended.
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Antibacterianos , Proteínas de Bactérias , Escherichia coli , Fezes , Tipagem de Sequências Multilocus , Ursidae , beta-Lactamases , Animais , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , beta-Lactamases/genética , Ursidae/microbiologia , China , Antibacterianos/farmacologia , Fezes/microbiologia , Proteínas de Bactérias/genética , Ecossistema , Filogenia , Testes de Sensibilidade Microbiana , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana/genéticaRESUMO
The aberrant activation of RAS/RAF/MEK/ERK signaling is important for KIT mutation-mediated tumorigenesis of gastrointestinal stromal tumor (GIST). In this study, we found that inhibition of RAF1 suppresses the activation of both wild-type KIT and primary KIT mutations in GIST, with primary KIT mutations showing greater sensitivity. This suggests a positive feedback loop between KIT and RAF1, wherein RAF1 facilitates KIT signaling. We further demonstrated that RAF1 associates with KIT and the kinase activity of RAF1 is necessary for its contribution to KIT activation. Accordingly, inhibition of RAF1 suppressed cell survival, proliferation, and cell cycle progression in vitro mediated by both wild-type KIT and primary KIT mutations. Inhibition of RAF1 in vivo suppressed GIST growth in a transgenic mouse model carrying germline KIT/V558A mutation, showing a similar treatment efficiency as imatinib, the first-line targeted therapeutic drug of GIST, while the combination use of imatinib and RAF1 inhibitor further suppressed tumor growth. Acquisition of drug-resistant secondary mutation of KIT is a major cause of treatment failure of GIST following targeted therapy. Like wild-type KIT and primary KIT mutations, inhibition of RAF1 suppressed the activation of secondary KIT mutation, and the cell survival, proliferation, cell cycle progression in vitro, and tumor growth in vivo mediated by secondary KIT mutation. However, the activation of secondary KIT mutation is less dependent on RAF1 compared with that of primary KIT mutations. Taken together, our results revealed that RAF1 facilitates KIT signaling and KIT mutation-mediated tumorigenesis of GIST, providing a rationale for further investigation into the use of RAF1 inhibitors alone or in combination with KIT inhibitor in the treatment of GIST, particularly in cases resistant to KIT inhibitors.
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Tumores do Estroma Gastrointestinal , Proteínas Proto-Oncogênicas c-kit , Proteínas Proto-Oncogênicas c-raf , Transdução de Sinais , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Animais , Proteínas Proto-Oncogênicas c-raf/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Humanos , Camundongos , Camundongos Transgênicos , Proliferação de Células , Linhagem Celular Tumoral , Mutação , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismoRESUMO
BACKGROUND: Previous studies have reported an increasing prevalence of childhood allergic rhinitis in developing countries. There is still a lack of the recent epidemiology of allergic rhinitis among Chinese preschool children. Therefore, this study explored the prevalence of rhinitis symptoms and identified their associations with potential risk factors among children at the age of 3-6 in Shanghai, China. METHODS: Validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was adopted to collect information about rhinitis symptoms and potential risk factors. Univariate and multivariate logistic regression analyses were used to assess associations between risk factors and allergic rhinitis and rhinoconjunctivitis. RESULTS: A total of 6183 questionnaires were included in our study. The prevalence of rhinitis ever, current rhinitis, and physician-diagnosed rhinitis were 32.6%, 29.2%, and 14.3%, respectively, while the prevalence of current rhinoconjunctivitis was 11.3%. The higher prevalence was observed in boys than in girls in terms of rhinitis ever, current rhinitis, current rhinoconjunctivitis and doctor-diagnosed rhinitis. Autumn had the highest prevalence among four seasons. In our multivariate logistic regression analyses, history of allergic diseases and paracetamol use in the last year showed positive associations with the increased risk of both current rhinitis and rhinoconjunctivitis, and antibiotic use was an independent significant risk factor only for current rhinitis. Genetic factors, including maternal and paternal rhinitis, asthma, and eczema, were significantly associated with the prevalence of current rhinitis. Similar associations were seen between these factors and current rhinoconjunctivitis, except for paternal eczema. Among environmental factors, smoking exposure at home, heavy truck traffic in home's street, floor heating system were independent risk factors for both current rhinitis and rhinoconjunctivitis in the adjusted model, while cleaning the house less than once a week was only associated with current rhinitis. CONCLUSION: The prevalence of current rhinitis was 29.2% among children aged 3-6 in Shanghai, China. Sex differences and seasonal variations were observed in the prevalence of rhinitis symptoms. The identified risk factors would provide a basis for policy makers and medical experts to take intervention measures to prevent allergic rhinitis and rhinoconjunctivitis.
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Asma , Conjuntivite Alérgica , Eczema , Rinite Alérgica , Rinite , Humanos , Feminino , Pré-Escolar , Masculino , Conjuntivite Alérgica/epidemiologia , Conjuntivite Alérgica/etiologia , China/epidemiologia , Rinite/complicações , Fatores de Risco , Eczema/epidemiologia , Rinite Alérgica/epidemiologia , Rinite Alérgica/complicações , Asma/complicações , Inquéritos e Questionários , PrevalênciaRESUMO
Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine-induced anti-tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free-field based whole-body ultrasound (US)-driven nanovaccines are constructed, named G5-CHC-R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small-sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia-sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5-CHC-R under a free-field based whole-body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5-CHC-R triggered by US represented a superior alternative for noninvasive irradiation of deep-seated tumors and magnification of local immune responses via driving mass release of tumor antigens and "cold-warm-hot" three-state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti-tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono-nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.
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Vacinas Anticâncer , Neoplasias , Animais , Nanovacinas , Ultrassonografia , Imunidade Adaptativa , Adjuvantes Imunológicos , Neoplasias/diagnóstico por imagem , Neoplasias/terapiaRESUMO
Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/ß-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and ß-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/ß-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/ß-Catenin signaling.
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Fatores de Transcrição SOXF , Proteínas de Xenopus , beta Catenina , Animais , Humanos , beta Catenina/genética , Células Endoteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo , Via de Sinalização Wnt , Xenopus/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismoRESUMO
The medium-chain dehydrogenase/reductase (MDR) superfamily contains many members that are widely present in organisms and play important roles in growth, metabolism, and stress resistance but have not been studied in Trichosporon asahii. In this study, bioinformatics and RNA sequencing methods were used to analyze the MDR superfamily of T. asahii and its regulatory effect on fluconazole resistance. A phylogenetic tree was constructed using Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, and T. asahii, and 73 MDRs were identified, all of which contained NADPH-binding motifs. T. asahii contained 20 MDRs that were unevenly distributed across six chromosomes. T. asahii MDRs (TaMDRs) had similar 3D structures but varied greatly in their genetic evolution at different phylum levels. RNA-seq and gene expression analyses revealed that the fluconazole-resistant T. asahii strain upregulates xylitol dehydrogenase, and downregulated alcohol dehydrogenase and sorbitol dehydrogenase concluded that the fluconazole-resistant T. asahii strain was less selective toward carbon sources and had higher adaptability to the environment. Overall, our study contributes to our understanding of TaMDRs, providing a basis for further analysis of the genes associated with drug resistance in T. asahii.
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Introduction: The giant panda (Ailuropoda melanoleuca) reproduction is of worldwide attention, and the vaginal microbiome is one of the most important factors affecting the reproductive rate of giant pandas. The aim of this study is to investigate the diversity of vaginal mycobiota structure, and potential pathogenic fungi in female giant pandas during estrus and non-estrus. Methods: This study combined with high-throughput sequencing and laboratory testing to compare the diversity of the vaginal mycobiota in giant pandas during estrus and non-estrus, and to investigate the presence of potentially pathogenic fungi. Potentially pathogenic fungi were studied in mice to explore their pathogenicity. Results and discussion: The results revealed that during estrus, the vaginal secretions of giant pandas play a crucial role in fungal colonization. Moreover, the diversity of the vaginal mycobiota is reduced and specificity is enhanced. The abundance of Trichosporon and Cutaneotrichosporon in the vaginal mycobiota of giant pandas during estrus was significantly higher than that during non-estrus periods. Apiotrichum and Cutaneotrichosporon were considered the most important genera, and they primarily originate from the environment owing to marking behavior exhibited during the estrous period of giant pandas. Trichosporon is considered a resident mycobiota of the vagina and is an important pathogen that causes infection when immune system is suppressed. Potentially pathogenic fungi were further isolated and identified from the vaginal secretions of giant pandas during estrus, and seven strains of Apiotrichum (A. brassicae), one strain of Cutaneotrichosporon (C. moniliiforme), and nine strains of Trichosporon (two strains of T. asteroides, one strain of T. inkin, one strain of T. insectorum, and five strains of T. japonicum) were identified. Pathogenicity results showed that T. asteroides was the most pathogenic strain, as it is associated with extensive connective tissue replacement and inflammatory cell infiltration in both liver and kidney tissues. The results of this study improve our understanding of the diversity of the vaginal fungi present in giant pandas and will significantly contribute to improving the reproductive health of giant pandas in the future.
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The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.
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Proteínas Morfogenéticas Ósseas , Proteínas de Transporte , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Organizadores Embrionários/metabolismo , Xenopus laevis/metabolismo , Padronização Corporal/fisiologia , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
Exploring the responses of root morphology and its physiological mechanisms under drought stress is significant for further improving water and nutrient absorption in roots. Here, we simulated drought through hydroponics combined with PEG treatments in tobacco to characterize the changes in tobacco root architecture. Our results showed the total root length, first lateral root number, and first lateral root length were significantly reduced upon increasing drought severity, but the average root diameter and secondary lateral root density increased under certain drought conditions. The change of auxin content in roots under drought stress was correlated with the root diameter and second lateral root density responses. Exogenous addition of the auxin analog (NAA) and the auxin transport inhibitor (NPA), as well as DR5:GUS staining experiments further demonstrated that auxin participated in this physiological process. Meanwhile, brassinolide (BR) exhibited a similar trend. Exogenous addition of BR (EBR) and the BR synthesis inhibitor BRZ experiments demonstrated that BR may participate upstream of auxin under drought stress. PEG treatment significantly up-regulated NtBRI1 at 9-24 h, and promoted the up-regulation of NtBSK2 and NtBSK3 at 48 h and 24 h, respectively, these genes may contribute to the change in root morphology under drought stress. This study shows that auxin and BR are involved in the changes in root morphology in tobacco exposed to drought stress. The elucidation of the molecular mechanism at play thus represents a future target for breeding drought-tolerant tobacco varieties.
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Secas , Nicotiana , Melhoramento Vegetal , Ácidos Indolacéticos/farmacologia , Transporte Biológico , Raízes de PlantasRESUMO
Trichosporon asahii is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underlying mechanisms. Therefore, this study aims to delineate the fluconazole resistance mechanisms of T. asahii and explore farnesol's effects on these processes. A comparative metabolome-transcriptome analysis of untreated fluconazole-sensitive (YAN), fluconazole-resistant (PB) T. asahii strains, and 25 µM farnesol-treated strains (YAN-25 and PB-25, respectively) was performed. The membrane lipid-related genes and metabolites were upregulated in the PB vs. YAN and PB-25 vs. PB comparisons. Farnesol demonstrated strain-dependent mechanisms underlying fluconazole tolerance between the YAN and PB strains, and upregulated and downregulated efflux pumps in PB-25 and YAN-25 strains, respectively. Membrane lipid-related metabolites were highly correlated with transporter-coding genes. Fluconazole resistance in T. asahii was induced by membrane lipid bio-synthesis activation. Farnesol inhibited fluconazole resistance in the sensitive strain, but enhanced resistance in the resistant strain by upregulating efflux pump genes and membrane lipids. This study offers valuable insights into the mechanisms underlying fungal drug resistance and provides guidance for future research aimed at developing more potent antifungal drugs for clinical use.
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BACKGROUND: Energy homeostasis is essential for the adaptation of animals to their environment and some wild animals keep low metabolism adaptive to their low-nutrient dietary supply. Giant panda is such a typical low-metabolic mammal exhibiting species specialization of extremely low daily energy expenditure. It has low levels of basal metabolic rate, thyroid hormone, and physical activities, whereas the cellular bases of its low metabolic adaptation remain rarely explored. RESULTS: In this study, we generate a single-nucleus transcriptome atlas of 21 organs/tissues from a female giant panda. We focused on the central metabolic organ (liver) and dissected cellular metabolic status by cross-species comparison. Adaptive expression mode (i.e., AMPK related) was prominently displayed in the hepatocyte of giant panda. In the highest energy-consuming organ, the heart, we found a possibly optimized utilization of fatty acid. Detailed cell subtype annotation of endothelial cells showed the uterine-specific deficiency of blood vascular subclasses, indicating a potential adaptation for a low reproductive energy expenditure. CONCLUSIONS: Our findings shed light on the possible cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas and helped to understand physiological adaptation response to nutrient stress.
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Ursidae , Animais , Feminino , Ursidae/genética , Ursidae/metabolismo , Transcriptoma , Células Endoteliais , Animais Selvagens , Exercício FísicoRESUMO
Peroxidase genes (Prdx) encode a family of antioxidant proteins, which can protect cells from oxidative damage by reducing various cellular peroxides. This study investigated the spatiotemporal expression patterns of gene members in this family during the early development of Xenopus tropicalis. Real-time quantitative PCR showed that all members of this gene family have a distinct temporal expression pattern during the early development of X. tropicalis embryos. Additionally, whole mount in situ hybridization revealed that individual prdx genes display differential expression patterns, with overlapping expression in lymphatic vessels, pronephros, proximal tubule, and branchial arches. This study provides a basis for further study of the function of the prdx gene family.
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Desenvolvimento Embrionário , Proteínas de Xenopus , Animais , Xenopus , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Xenopus laevis/genéticaRESUMO
BACKGROUND: Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. METHODS: Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. RESULTS: After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (ß = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (ß = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (ß = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4). CONCLUSIONS: Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.
Assuntos
Esquizofrenia , Humanos , Esquizofrenia/genética , Análise da Randomização Mendeliana , Encéfalo , Inflamação , Fenótipo , Estudo de Associação Genômica AmplaRESUMO
BACKGROUND: The gut microbiota of the giant panda (Ailuropoda melanoleuca), a global symbol of conservation, are believed to be involved in the host's dietary switch to a fibrous bamboo diet. However, their exact roles are still largely unknown. RESULTS: In this study, we first comprehensively analyzed a large number of gut metagenomes giant pandas (n = 322), including 98 pandas sequenced in this study with deep sequencing (Illumina) and third-generation sequencing (nanopore). We reconstructed 408 metagenome-assembled genomes (MAGs), and 148 of which (36.27%) were near complete. The most abundant MAG was classified as Streptococcus alactolyticus. A pairwise comparison of the metagenomes and meta-transcriptomes in 14 feces revealed genes involved in carbohydrate metabolism were lower, but those involved in protein metabolism were greater in abundance and expression in giant pandas compared to those in herbivores and omnivores. Of note, S. alactolyticus was positively correlated to the KEGG modules of essential amino-acid biosynthesis. After being isolated from pandas and gavaged to mice, S. alactolyticus significantly increased the relative abundance of essential amino acids in mice jejunum. CONCLUSIONS: The study highlights the unique protein metabolic profiles in the giant panda's gut microbiome. The findings suggest that S. alactolyticus is an important player in the gut microbiota that contributes to the giant panda's dietary adaptation by more involvement in protein rather than carbohydrate metabolism. Video Abstract.