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1.
Front Microbiol ; 15: 1409497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234555

RESUMO

Introduction: Observational studies suggest associations between gut microbiota and polymyositis (PM) and dermatomyositis (DM), but causal relationships are unclear. We investigate the causal effects of gut microbiota on PM and DM, providing insights hoping to provide insights for future treatment and prevention. Methods: Summary statistics of gut microbiota were obtained from a multi-ethnic Genome Wide Association Studies (GWAS) meta-analysis, including 119 taxa from 18,340 Europeans. PM/DM statistics were extracted from GWAS analyses. Mendelian randomization (MR) with IVW, MR-Egger, and weighted median methods was performed. Sensitivity analyses addressed heterogeneity and pleiotropy. Of the 119 bacterial genera studied, six showed causal links. Results: Alloprevotella (OR: 3.075, 95% CI: 1.127-8.386, p = 0.028), Ruminococcaceae UCG003 (OR: 4.219, 95% CI: 1.227-14.511, p = 0.022), Dialister (OR: 0.273, 95% CI: 0.077-0.974, p = 0.045) were associated with PM. Anaerotruncus (OR: 0.314, 95% CI: 0.112-0.882, p = 0.028), Ruminococcaceae UCG002 (OR: 2.439, 95% CI: 1.173-5.071, p = 0.017), Sutterella (OR: 3.392, 95% CI: 1.302-8.839, p = 0.012) were related to DM. Sensitivity analyses validated these associations. Discussion: We establish causal relationships between Ruminococcaceae, Sutterella, Anaerotruncus with DM, Alloprevotella, Ruminococcaceae UCG003, and Dialister with PM. Common microbiota, like Ruminococcaceae, have significant clinical implications. These findings open up greater possibilities for the gut microbiota to contribute to the development of PM/DM and for future monitoring of the gut microbiota in patients with PM/DM.

2.
Cell Death Dis ; 15(7): 516, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025830

RESUMO

Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.


Assuntos
Proliferação de Células , Glucose , Glucosefosfato Desidrogenase , Neoplasias de Mama Triplo Negativas , Regulação para Cima , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Humanos , Feminino , Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/genética , Animais , Linhagem Celular Tumoral , Camundongos , Glucose/metabolismo , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus
3.
Int J Cancer ; 155(3): 545-557, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561936

RESUMO

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.


Assuntos
Neoplasias da Mama , COVID-19 , Fator Estimulador de Colônias de Granulócitos , Análise da Randomização Mendeliana , SARS-CoV-2 , Humanos , COVID-19/virologia , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Pessoa de Meia-Idade , SARS-CoV-2/genética , Idoso , Adulto , Estudos Prospectivos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Estudos de Coortes
4.
Exp Gerontol ; 191: 112434, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38636571

RESUMO

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.


Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 1 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoporose , Polimorfismo de Nucleotídeo Único , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/complicações , Osteoporose/genética , Densidade Óssea/genética , Fatores de Risco , Feminino , Masculino , Colo do Fêmur/diagnóstico por imagem , Predisposição Genética para Doença , Vértebras Lombares , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Antebraço
5.
Mar Biotechnol (NY) ; 26(3): 475-487, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602600

RESUMO

Prorocentrum lima, a widely distributed dinoflagellate known for its production of harmful biotoxins, poses a significant threat to humans, aquaculture, and marine ecosystems. As a result, the detection of this toxic alga in coastal waters has become an urgent research focus. In this study, a rapid, sensitive, and cost-effective detection method based on loop-mediated isothermal amplification (LAMP) was developed to identify P. lima. In this method, cell extracts of P. lima were diluted and used directly as templates for amplification, eliminating the need for nucleic acid purification and simplifying the detection process. Hydroxy naphthol blue (HNB) was incorporated into the reaction mix to facilitate result interpretation, enabling visual determination of the amplification outcome with the naked eye. The entire detection process, from DNA extraction to template amplification and product detection, could be completed within 80 min using a simple constant temperature-control device. This LAMP-based detection method demonstrated excellent reliability, specificity, and a low detection limit of 5.87 cells/mL for DNA crude extract. The assay offered an efficient alternative to PCR for rapid detection of P. lima. By streamlining the detection process and offering a visual readout, this technique holds promise for efficient and routine monitoring of harmful algal species, benefitting both research efforts and environmental management strategies.


Assuntos
Dinoflagellida , Técnicas de Amplificação de Ácido Nucleico , Dinoflagellida/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Naftalenossulfonatos , Limite de Detecção , Reprodutibilidade dos Testes , Técnicas de Diagnóstico Molecular
6.
Microorganisms ; 12(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38674651

RESUMO

Isoprenoids and their derivatives, essential for all cellular life on Earth, are particularly crucial in archaeal membrane lipids, suggesting that their biosynthesis pathways have ancient origins and play pivotal roles in the evolution of early life. Despite all eukaryotes, archaea, and a few bacterial lineages being known to exclusively use the mevalonate (MVA) pathway to synthesize isoprenoids, the origin and evolutionary trajectory of the MVA pathway remain controversial. Here, we conducted a thorough comparison and phylogenetic analysis of key enzymes across the four types of MVA pathway, with the particular inclusion of metagenome assembled genomes (MAGs) from uncultivated archaea. Our findings support an archaeal origin of the MVA pathway, likely postdating the divergence of Bacteria and Archaea from the Last Universal Common Ancestor (LUCA), thus implying the LUCA's enzymatic inability for isoprenoid biosynthesis. Notably, the Asgard archaea are implicated in playing central roles in the evolution of the MVA pathway, serving not only as putative ancestors of the eukaryote- and Thermoplasma-type routes, but also as crucial mediators in the gene transfer to eukaryotes, possibly during eukaryogenesis. Overall, this study advances our understanding of the origin and evolutionary history of the MVA pathway, providing unique insights into the lipid divide and the evolution of early life.

7.
Syst Appl Microbiol ; 47(2-3): 126490, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38330528

RESUMO

In this study we describe the first cultured representative of Candidatus Synoicihabitans genus, a novel strain designated as LMO-M01T, isolated from deep-sea sediment of South China Sea. This bacterium is a facultative aerobe, Gram-negative, non-motile, and has a globular-shaped morphology, with light greenish, small, and circular colonies. Analysis of the 16S rRNA gene sequences of strain LMO-M01T showed less than 93% similarity to its closest cultured members. Furthermore, employing advanced phylogenomic methods such as comparative genome analysis, average nucleotide identity (ANI), average amino acids identity (AAI), and digital DNA-DNA hybridization (dDDH), placed this novel species within the candidatus genus Synoicihabitans of the family Opitutaceae, Phylum Verrucomicrobiota. The genomic analysis of strain LMO-M01T revealed 175 genes, encoding putative carbohydrate-active enzymes. This suggests its metabolic potential to degrade and utilize complex polysaccharides, indicating a significant role in carbon cycling and nutrient turnover in deep-sea sediment. In addition, the strain's physiological capacity to utilize diverse biopolymers such as lignin, xylan, starch, and agar as sole carbon source opens up possibilities for sustainable energy production and environmental remediation. Moreover, the genome sequence of this newly isolated strain has been identified across diverse ecosystems, including marine sediment, fresh water, coral, soil, plants, and activated sludge highlighting its ecological significance and adaptability to various environments. The recovery of strain LMO-M01T holds promise for taxonomical, ecological and biotechnological applications. Based on the polyphasic data, we propose that this ecologically important strain LMO-M01T represents a novel genus (previously Candidatus) within the family Opitutaceae of phylum Verrucomicrobiota, for which the name Synoicihabitans lomoniglobus gen. nov., sp. nov. was proposed. The type of strain is LMO-M01T (= CGMCC 1.61593T = KCTC 92913T).


Assuntos
DNA Bacteriano , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Sedimentos Geológicos/microbiologia , China , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Água do Mar/microbiologia , Hibridização de Ácido Nucleico , Técnicas de Tipagem Bacteriana , Genoma Bacteriano/genética , Composição de Bases , Ácidos Graxos/análise
8.
BMC Med Genomics ; 16(1): 237, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814247

RESUMO

BACKGROUND: Growing evidence supports an association between physical activity (PA) and the risk of osteoarthritis (OA), but this may be influenced by confounding and reverse causality. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to reveal the causal relationship between PA and OA. METHODS: MR was performed to explore the causation of PA and OA with genetic variants as instrumental variables. The genetic variants were derived from the summary statistics of a large genome-wide association study meta-analysis based on the European population (n = 661,399), including self-reported leisure screen time (LST) and moderate-to-vigorous physical activity (MVPA), and Arthritis Research UK Osteoarthritis Genetics Consortium cohorts (417,596, 393,873 and 403,124 for overall, hip and knee OA, respectively). The major MR analysis used in this work was the inverse variance weighted (IVW) approach, and sensitivity, pleiotropy, and heterogeneity studies were performed to evaluate the validity of the findings. RESULTS: IVW estimates indicated that LST had a risk effect on overall OA (odds ratio (OR) = 1.309, 95% confidence interval (CI): 1.198-1.430, P = 2.330 × 10-9), hip OA (OR = 1.132, 95% CI: 1.009-1.269, P = 0.034) and knee OA (OR = 1.435. 95% CI: 1.286-1.602, P = 1.225 × 10-10). In contrast, no causal relationship was found between MVPA and OA (overall OA: OR = 0.895, 95% CI: 0.664-1.205, P = 0.465; hip OA: OR = 1.189, 95% CI: 0.792-1.786, P = 0.404; knee OA: OR = 0.707, 95% CI: 0.490 -1.021, P = 0.064). In addition, we observed significant heterogeneity in instrumental variables, but no horizontal pleiotropy was detected. CONCLUSIONS: Recent findings demonstrated a protective impact of reducing LST on OA, independent of MVPA. This provides valuable insights into the role of physical activity in OA and offers lifestyle recommendations, such as reducing recreational sedentary behaviors and promoting appropriate exercise, for individuals at risk of OA.


Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Exercício Físico , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoartrite do Quadril/genética , Osteoartrite do Joelho/genética , Polimorfismo de Nucleotídeo Único
9.
Artigo em Inglês | MEDLINE | ID: mdl-37486324

RESUMO

A novel member of class Alphaproteobacteria was isolated from marine sediment of the South China Sea. Cells of strain LMO-2T were Gram-stain negative, greyish in colour, motile, with a single lateral flagellum and short rod in shape with a slight curve. Strain LMO-2T was positive for oxidase and negative for catalase. The bacterium grew aerobically at 10-40 °C (optimum, 25-30 °C), pH 5.5-10.0 (optimum, pH 7.0) and 0-9 % NaCl (w/v; optimum, 2-3 %). Phylogenetic analysis of the 16S rRNA gene sequence and phylogenomic analysis of the whole genome sequence indicated that strain LMO-2T represents a new genus and a new species within the family Devosiaceae, class Alphaproteobacteria, phylum Pseudomonadota. Comparisons of the 16S rRNA gene sequences of strain LMO-2T showed 94.8 % similarity to its closest relative. The genome size is ~3.45 Mbp with a DNA G+C content of 58.17 mol%. The strain possesses potential capability for the degradation of complex organic matter, i.e. fatty acid and benzoate. The predominant cellular fatty acids (>10 %) were C16 : 0 and C18 : 1 ω7c 11-methyl. The sole respiratory quinone was ubiquinone-10. The major identified polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phospholipid. Based on the polyphasic taxonomic data, strain LMO-2T represents a novel genus and a novel species for which the name Mariluticola halotolerans gen. nov., sp. nov., was proposed in the family Devosiaceae. The type strain is LMO-2T (=CGMCC 1.19273T=JCM 34934T).


Assuntos
Alphaproteobacteria , Ácidos Graxos , Ácidos Graxos/química , Água do Mar/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Composição de Bases , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos/química , China
10.
Sci Adv ; 9(27): eadf5069, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37406125

RESUMO

Bathyarchaeia, as one of the most abundant microorganisms on Earth, play vital roles in the global carbon cycle. However, our understanding of their origin, evolution, and ecological functions remains poorly constrained. Here, we present the largest dataset of Bathyarchaeia metagenome assembled genome to date and reclassify Bathyarchaeia into eight order-level units corresponding to the former subgroup system. Highly diversified and versatile carbon metabolisms were found among different orders, particularly atypical C1 metabolic pathways, indicating that Bathyarchaeia represent overlooked important methylotrophs. Molecular dating results indicate that Bathyarchaeia diverged at ~3.3 billion years, followed by three major diversifications at ~3.0, ~2.5, and ~1.8 to 1.7 billion years, likely driven by continental emergence, growth, and intensive submarine volcanism, respectively. The lignin-degrading Bathyarchaeia clade emerged at ~300 million years perhaps contributed to the sharply decreased carbon sequestration rate during the Late Carboniferous period. The evolutionary history of Bathyarchaeia potentially has been shaped by geological forces, which, in turn, affected Earth's surface environment.


Assuntos
Carbono , Redes e Vias Metabólicas , Carbono/metabolismo
11.
BMC Cancer ; 23(1): 377, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098487

RESUMO

BACKGROUND: Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated. METHODS: The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan-Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models. RESULTS: BC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038-1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163-4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218-4.913], P = 0.011). CONCLUSIONS: For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.


Assuntos
Neoplasias da Mama , DNA Mitocondrial , Humanos , Feminino , DNA Mitocondrial/genética , Variações do Número de Cópias de DNA , Neoplasias da Mama/genética , Prognóstico , Leucócitos
12.
Microbiome ; 11(1): 81, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081504

RESUMO

BACKGROUND: A large proportion of prokaryotic microbes in marine sediments remains uncultured, hindering our understanding of their ecological functions and metabolic features. Recent environmental metagenomic studies suggested that many of these uncultured microbes contribute to the degradation of organic matter, accompanied by acetogenesis, but the supporting experimental evidence is limited. RESULTS: Estuarine sediments were incubated with different types of organic matters under anaerobic conditions, and the increase of uncultured bacterial populations was monitored. We found that (1) lignin stimulated the increase of uncultured bacteria within the class Dehalococcoidia. Their ability to metabolize lignin was further supported by the presence of genes associated with a nearly complete degradation pathway of phenolic monomers in the Dehalococcoidia metagenome-assembled genomes (MAGs). (2) The addition of cellulose stimulated the increase of bacteria in the phylum Ca. Fermentibacterota and family Fibrobacterales, a high copy number of genes encoding extracellular endoglucanase or/and 1,4-beta-cellobiosidase for cellulose decomposition and multiple sugar transporters were present in their MAGs. (3) Uncultured lineages in the order Bacteroidales and the family Leptospiraceae were enriched by the addition of casein and oleic acid, respectively, a high copy number of genes encoding extracellular peptidases, and the complete ß-oxidation pathway were found in those MAGs of Bacteroidales and Leptospiraceae, respectively. (4) The growth of unclassified bacteria of the order Clostridiales was found after the addition of both casein and cellulose. Their MAGs contained multiple copies of genes for extracellular peptidases and endoglucanase. Additionally, 13C-labeled acetate was produced in the incubations when 13C-labeled dissolved inorganic carbon was provided. CONCLUSIONS: Our results provide new insights into the roles of microorganisms during organic carbon degradation in anaerobic estuarine sediments and suggest that these macro and single molecular organic carbons support the persistence and increase of uncultivated bacteria. Acetogenesis is an additional important microbial process alongside organic carbon degradation. Video Abstract.


Assuntos
Carbono , Celulase , Carbono/metabolismo , Lignina/metabolismo , Anaerobiose , Caseínas/genética , Caseínas/metabolismo , Celulase/genética , Celulase/metabolismo , Bactérias/genética , Bactérias/metabolismo , Peptídeo Hidrolases/genética , Sedimentos Geológicos/microbiologia , Filogenia
13.
Front Neurol ; 14: 1105616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846119

RESUMO

Objective: This study aims to establish a radiomics-based machine learning model that predicts the risk of transient ischemic attack in patients with mild carotid stenosis (30-50% North American Symptomatic Carotid Endarterectomy Trial) using extracted computed tomography radiomics features and clinical information. Methods: A total of 179 patients underwent carotid computed tomography angiography (CTA), and 219 carotid arteries with a plaque at the carotid bifurcation or proximal to the internal carotid artery were selected. The patients were divided into two groups; patients with symptoms of transient ischemic attack after CTA and patients without symptoms of transient ischemic attack after CTA. Then we performed random sampling methods stratified by the predictive outcome to obtain the training set (N = 165) and testing set (N = 66). 3D Slicer was employed to select the site of plaque on the computed tomography image as the volume of interest. An open-source package PyRadiomics in Python was used to extract radiomics features from the volume of interests. The random forest and logistic regression models were used to screen feature variables, and five classification algorithms were used, including random forest, eXtreme Gradient Boosting, logistic regression, support vector machine, and k-nearest neighbors. Data on radiomic feature information, clinical information, and the combination of these pieces of information were used to generate the model that predicts the risk of transient ischemic attack in patients with mild carotid artery stenosis (30-50% North American Symptomatic Carotid Endarterectomy Trial). Results: The random forest model that was built based on the radiomics and clinical feature information had the highest accuracy (area under curve = 0.879; 95% confidence interval, 0.787-0.979). The combined model outperformed the clinical model, whereas the combined model showed no significant difference from the radiomics model. Conclusion: The random forest model constructed with both radiomics and clinical information can accurately predict and improve discriminative power of computed tomography angiography in identifying ischemic symptoms in patients with carotid atherosclerosis. This model can aid in guiding the follow-up treatment of patients at high risk.

14.
mLife ; 2(3): 272-282, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38817817

RESUMO

Lignin degradation is a major process in the global carbon cycle across both terrestrial and marine ecosystems. Bathyarchaeia, which are among the most abundant microorganisms in marine sediment, have been proposed to mediate anaerobic lignin degradation. However, the mechanism of bathyarchaeial lignin degradation remains unclear. Here, we report an enrichment culture of Bathyarchaeia, named Candidatus Baizosediminiarchaeum ligniniphilus DL1YTT001 (Ca. B. ligniniphilus), from coastal sediments that can grow with lignin as the sole organic carbon source under mesophilic anoxic conditions. Ca. B. ligniniphilus possesses and highly expresses novel methyltransferase 1 (MT1, mtgB) for transferring methoxyl groups from lignin monomers to cob(I)alamin. MtgBs have no homology with known microbial methyltransferases and are present only in bathyarchaeial lineages. Heterologous expression of the mtgB gene confirmed O-demethylation activity. The mtgB genes were identified in metagenomic data sets from a wide range of coastal sediments, and they were highly expressed in coastal sediments from the East China Sea. These findings suggest that Bathyarchaeia, capable of O-demethylation via their novel and specific methyltransferases, are ubiquitous in coastal sediments.

15.
BMC Cancer ; 22(1): 1125, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324133

RESUMO

BACKGROUND: Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services. METHODS: The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction. RESULTS: Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02). CONCLUSION: This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias da Mama/patologia , Mutação em Linhagem Germinativa , Predisposição Genética para Doença , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/patologia , Células Germinativas/patologia , Redes Neurais de Computação , China
16.
Front Plant Sci ; 13: 1059925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407632

RESUMO

The MIKCC-type gene family plays important roles in plant growth, development, and tolerance of biotic and abiotic stress, especially during floral organ differentiation. However, there have been no studies of MIKCC-type genes in rose, and functional differentiation of family members has not been explored. In this study, we identified 42 MIKCC-type genes in rose, classified the genes into 12 subfamilies, and constructed a phylogenetic tree. We performed expression analysis of these genes, and found that expression patterns correlated with the predicted subfamily, indicating that the features of MIKCC-type genes were broadly conserved during evolution. Collinear analysis of MIKCC genes among Rosaceae species confirmed the occurrence of whole genome duplications (WGD) and revealed some species-specific MIKCC genes. Transcriptome analysis showed that the expression of some MIKCC-type genes responded to low temperatures (4°C, 24 h) during flower organ differentiation. These conserved, duplicated, and novel expression patterns of MIKCC-type genes may have facilitated the adaptation of rose to various internal and external environmental changes. The results of this study provide a theoretical basis for future functional analysis of the MIKCC genes in rose and investigation of the evolutionary pattern of the MIKCC gene family in the Rosaceae genome.

17.
Hereditas ; 159(1): 33, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085074

RESUMO

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are generally lacking in the Chinese population. Mutated genes in this disease can estimate the risk of malignant transformation in GCMN. Therefore, it is worth investigating the genetic information of GCMN. METHODS: Here, we presented two cases of GCMN of the upper extremities. The clinical and histological data were analyzed. The whole exome sequencing (WES) was performed to investigate the mutational profile of peripheral venous blood (PB), normal skin (NS), small melanocytic nevus (SMN), deep penetrating and non-penetrating GCMN (dPGCMN and nPGCMN). RESULTS: We showed a reduction in the circumference of involved upper extremities in both patients. The clinical and histopathological data indicated the reduction of adipose tissue associated with the invasion of GCMN. The WES data revealed that MUC16, MAP3K15 and ABCA1 were novel potential candidate genes for the disease as well as biomarkers for predicting malignant transformation. CONCLUSION: The MUC16, MAP3K15 and ABCA1 may serve as novel biomarkers for predicting malignant transformation and targets for the diagnoses and therapy for the GCMN.


Assuntos
Nevo Pigmentado , Neoplasias Cutâneas , Transportador 1 de Cassete de Ligação de ATP , Antígeno Ca-125 , Humanos , Proteínas de Membrana/genética , Mutação , Nevo Pigmentado/genética , Neoplasias Cutâneas/genética , Sequenciamento do Exoma
18.
Sci Total Environ ; 848: 157590, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-35901888

RESUMO

Intermittent increases of dissolved ferrous iron concentrations have been observed in deep marine methanic sediments which is different from the traditional diagenetic electron acceptor cascade, where iron reduction precedes methanogenesis. Here we aimed to gain insight into the mechanism of iron reduction and the associated microbial processes in deep sea methanic sediment by setting up long-term high-pressure incubation experiments supplemented with ferrihydrite and methane. Continuous iron reduction was observed during the entire incubation period. Intriguingly, ferrihydrite addition shifted the archaeal community from the dominance of hydrogenotrophic methanogens (Methanogenium) to methylotrophic methanogens (Methanococcoides). The enriched samples were then amended with 13C-labeled methane and different iron (oxyhydr)oxides in batch slurries to test the mechanism of iron reduction. Intensive iron reduction was observed, the highest rates with ferrihydrite, followed by hematite and then magnetite, however, no anaerobic oxidation of methane (AOM) was observed in any treatment. Further tests on the enriched slurry showed that the addition of molybdate decreased iron reduction, suggesting a link between iron reduction with sulfur cycling. This was accompanied by the enrichment of microbes capable of dissimilatory sulfate reduction and sulfur/thiosulfate oxidation, which indicates the presence of a cryptic sulfur cycle in the incubation system with the addition of iron (oxyhydr)oxides. Our work suggests that under low sulfate conditions, the presence of iron (oxyhydr)oxides would trigger a cascade of microbial reactions, and iron reduction could link with the microbial sulfur cycle, changing the kinetics of the methanogenesis process in methanic sediment.


Assuntos
Ferro , Óxidos , Compostos Férricos , Óxido Ferroso-Férrico , Sedimentos Geológicos , Metano , Sulfatos , Enxofre , Tiossulfatos
19.
Front Pharmacol ; 13: 921718, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903336

RESUMO

Maximization of phototoxic damage on tumor is essential for effective anticancer photodynamic therapy (PDT). Highly cancer-cell-organelle-specific delivery of efficient photosensitizers (PSs) in vitro and in vivo is in great demand. In this paper, a novel water-soluble mitochondria targeted cationic bromopropylate imidazoliumyl axially substituted silicon (IV) phthalocyanine (Br-ID-SiPc) is developed to improve PDT efficiency by enhancing the subcellular localization of photosensitizers. Benefiting from the targeting capability of bromopropylate imidazoliumyl, Br-ID-SiPc can selectively accumulate in mitochondria after cellular uptake, this process could be tracked by two-photon imaging. Br-ID-SiPc effectively damaged the circular plasmid DNA of mitochondria and induced HO-8910 cells apoptosis. Our results indicate that Br-ID-SiPc is a potential photosensitizer which can be used as a mitochondria-targeting and two-photon fluorescent imaging molecule for PDT of cancers.

20.
Microbiol Resour Announc ; 11(5): e0019122, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35416693

RESUMO

Here, we report the draft genome sequences of four bacterial isolates from sediment of the South China Sea. Three of the isolates belong to the class Alphaproteobacteria and encode complete SoxXAYZBCD gene clusters, related to thiosulfate oxidation, while one isolate belongs to the class Opitutae and possesses a total of 397 carbohydrate active enzymes (CAZymes), related to predicted polysaccharide degradation.

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