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Kluyveromyces marxianus, a thermotolerant, fast-growing, Crabtree-negative yeast, is a promising chassis for the manufacture of various bioproducts. Although several genome editing tools are available for this yeast, these tools still require refinement to enable more convenient and efficient genetic modification. In this study, we engineered the K. marxianus NBRC 104275 strain by impairing the nonhomologous end joining and enhancing the homologous recombination machinery, which resulted in improved homology-directed repair effective on homology arms of up to 40 bp in length. Additionally, we simplified the CRISPR-Cas9 editing system by constructing a strain for integrative expression of Cas9 nuclease and plasmids bearing different selection markers for gRNA expression, thereby facilitating iterative genome editing without the need for plasmid curing. We demonstrated that tRNA was more effective than the hammerhead ribozyme for processing gRNA primary transcripts, and readily assembled tRNA-gRNA arrays were used for multiplexed editing of at least four targets. This editing tool was further employed for simultaneous scarless in vivo assembly of a 12-kb cassette from three fragments and marker-free integration for expressing a fusion variant of fatty acid synthase, as well as the integration of genes for starch hydrolysis. Together, the genome editing tool developed in this study makes K. marxianus more amenable to genetic modification and will facilitate more extensive engineering of this nonconventional yeast for chemical production.
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Microplastic records from lake cores can reconstruct the plastic pollution history. However, the associations between anthropogenic activities and microplastic accumulation are not well understood. Huguangyan Maar Lake (HML) is a deep-enclosed lake without inlets and outlets, where the sedimentary environment is ideal for preserving a stable and historical microplastic record. Microplastic (size: 10-500 µm) characteristics in the HML core were identified using the Laser Direct Infrared Imaging system. The earliest detectable microplastics appeared unit in 1955 (1.1 items g-1). The microplastic abundance ranged from n.d. to 615.2 items g-1 in 1955-2019 with an average of 134.9 items g-1. The abundance declined slightly during the 1970s and then increased rapidly after China's Reform and Opening Up in 1978. Sixteen polymer types were detectable, with polyethylene and polypropylene dominating, accounting for 23.5 and 23.3% of the total abundance, and the size at 10-100 µm accounted for 80%. Socioeconomic factors dominated the microplastic accumulation based on the random forest modeling, and the contributions of GDP per capita, plastic-related industry yield, and total crop yield were, respectively, 13.9, 35.1, and 9.3% between 1955-2019. The total crop yield contribution further increased by 1.7% after 1978. Coarse sediment particles increased with soil erosion exacerbated microplastics discharging into the sediment.
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Monitoramento Ambiental , Lagos , Microplásticos , China , Microplásticos/análise , Poluentes Químicos da Água/análise , Plásticos , Sedimentos Geológicos/químicaRESUMO
Lake sediment is a natural sink for polycyclic aromatic hydrocarbons (PAHs). PAH sedimentation characteristics and their impact factors of Chinese lakes have mainly been qualitative assessed. However, quantitative impacts of PAH sedimentation from different factors have not been well analyzed. To fill this gap, we screened PAH sedimentation records from the literature, for 51 lakes in China and other regions of the world, to identify historical concentration variation and the impact factors of PAHs in different regions, in lake sediment. The results show that PAH concentrations in the sediment core in the selected Chinese lakes (478 ± 812 ng/g dry weight (dw)) were significantly lower than those in North America (5518 ± 6572 ng/g dw) and Europe (3817 ± 4033 ng/g dw). From 1900 to 2015, most of the lakes in China showed an increasing trend of PAH sedimentation concentrations, with the lakes in Southeastern China showed a decreasing trend of PAH concentration in the period of 2001-2015, which was later than the peak times shown in Western countries (1941-1970). The 2-3-ring PAHs were the main components in the sediment core of Chinese lakes, but the proportion to the total PAHs decreased from 72% in 1900-1940 to 55% in 2001-2015. Generalized additive modeling (GAM) was adopted to simulate the associations between PAH sedimentation records and the impact factors. There are large regional variations of economic and industrial development in China. The impact factors of PAH accumulation in the lake sediments differ in different regions. However, population and the consumption of coal, pesticides, and fertilizer were identified to be the most important impact factors influencing PAH sedimentation. The Chinese government needs to strengthen control measures on pollutant discharge to reduce the anthropogenic impact of PAH sedimentation in lakes.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Lagos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos , ChinaRESUMO
Although reports of human infection with influenza A(H5N6) increased in 2021, reports of similar H5N6 virus infection in poultry are few. We detected 10 avian influenza A(H5N6) clade 2.3.4.4b viruses in poultry from 4 provinces in China. The viruses showed strong immune-escape capacity and complex genetic reassortment, suggesting further transmission risk.
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Vírus da Influenza A , Influenza Aviária , Influenza Humana , Animais , Aves , China/epidemiologia , Humanos , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Influenza Humana/epidemiologia , Filogenia , Aves Domésticas , Vírus Reordenados/genéticaRESUMO
RATIONALE: Ion mobility spectrometry (IMS) is a powerful analytical tool extensively applied in numerous domains. However, there still exists the phenomenon of peaks overlapping in the analysis of isomers with similar structures due to the limited resolution of IMS. In this paper, a dynamic inertia weight particle swarm optimization (DIWPSO) algorithm combined with second-order differentiation is proposed to separate the IMS overlapping peaks efficiently and precisely. METHODS: It can identify the component number of overlapping peaks and limit those parameters (ion mobility, intensity, and full-width at half maximum of each single peak) of the peak model in a small range using second-order differentiation. Based on this, DIWPSO that has been set the best operating parameters is capable of accurately separating IMS overlapping peaks to identify the compound within a short time. RESULTS: A comparison between the performance of DIWPSO and the improved particle swarm optimization (IPSO) found that DIWPSO with separation errors less than 2.34% overall outperforms IPSO whose maximum error is up to 5.58%. Moreover, the running time of DIWPSO is 30-80 times less than that of IPSO, and DIWPSO exhibits stronger robustness. CONCLUSIONS: This method can automatically identify the component number of IMS overlapping peaks and resolve them with muticomponents and different overlapped degrees rapidly and accurately, which further improves the structural resolution of IMS.
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Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.
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Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Pirazóis/administração & dosagem , Dermatopatias , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Resistência a Medicamentos/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Nitrilas , Pirimidinas , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/mortalidade , Esteroides/administração & dosagem , Taxa de SobrevidaRESUMO
Hemophagocytic lymphohistiocytosis with central nervous system involvement is caused by inflammatory factor storms. The inflammatory factors invade the blood-brain barrier and further infiltrate brain tissue resulting in associated neurological and/or psychiatric symptoms in hemophagocytic lymphohistiocytosis with central nervous system involvement patients. This case report is based on a 14-year-old male patient who experienced intermittent dizziness and blurred vision about five years before admission as well as lower limb weakness and unstable walking approximately three years before admission. His brain MRI showed abnormal signals in the bilateral cerebellar hemisphere and vermis, right occipital lobe, and bilateral basal ganglia. The cerebrospinal fluid examination revealed an increase in nucleated cells, mainly monocytes, and elevated protein. He had no typical manifestation of hemophagocytic lymphohistiocytosis in the early stage, such as fever, cytopenia, or hepatosplenomegaly. He was misdiagnosed with meningoencephalitis or tuberculous meningitis. Perforin gene detection revealed a mutation in the PRF1 gene. The final diagnosis of type 2 familial hemophagocytic lymphohistiocytosis was made based on the neurological symptoms and genetic test. The possibility of hemophagocytic lymphohistiocytosis needs to be considered in patients with unexplained central nervous system symptoms, even if the patient does not have typical hemophagocytic lymphohistiocytosis symptoms, such as fever, cytopenia, or hepatosplenomegaly. We present the neurological symptoms of familial hemophagocytic lymphohistiocytosis type 2.
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Encéfalo/patologia , Linfo-Histiocitose Hemofagocítica/diagnóstico por imagem , Linfo-Histiocitose Hemofagocítica/patologia , Adolescente , Encéfalo/diagnóstico por imagem , Humanos , Linfo-Histiocitose Hemofagocítica/genética , Imageamento por Ressonância Magnética , Masculino , Mutação , Perforina/genéticaRESUMO
Stressful life events especially the chronic unpredictable stress are the obvious precipitating factors of depression. The biological information transduction in cells plays an important role in the molecular biology mechanism of depression. Mitogen-activated protein kinase phosphatase-1 (MKP-1) regulates the cell physiological activity and involves in the adjustment of neural plasticity, function, and survival. This experiment tried to explore the possible effects of MKP-1 in hippocampus on depression of rats by determining the expression of MKP-1 mRNA and DNA methylation in MKP-1 gene promoter. The animal model was established by chronic unpredictable stress, and evaluated by open-field test and weight changes. All the rats were divided into the sham stimulation, the physiological saline, and the fluoxetine (1.25, 2.50, and 5.00 mg/kg) groups randomly. The expression of MKP-1 mRNA in the hippocampus was measured by RT-PCR and the methylation of MKP-1 promoter DNA was detected by COBRA. The chronic unpredicted stress (1) increased the animal movement scores in open-field test, and fluoxetine could prevent this increasement; (2) increased the body weight, and fluoxetine could not prevent this increasement; and (3) increased MKP-1 mRNA expression in the hippocampus, and fluoxetine could prevent it. However, fluoxetine did not influence the DNA methylation of MKP-1 gene promoter in the hippocampus during the chronic unpredicted stress. MKP-1 in the hippocampus might be involved in the etiology of depression, and DNA methylation of MKP-1 gene promoter in the hippocampus did not related with the depression.
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Metilação de DNA/genética , Depressão/enzimologia , Depressão/etiologia , Fosfatase 1 de Especificidade Dupla/genética , Hipocampo/enzimologia , Estresse Psicológico/complicações , Estresse Psicológico/enzimologia , Animais , Peso Corporal/efeitos dos fármacos , Doença Crônica , Metilação de DNA/efeitos dos fármacos , Depressão/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Fluoxetina/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Movimento , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Estresse Psicológico/genéticaRESUMO
Liquid crystal monomers (LCMs), a group of synthetic chemicals released from liquid crystal devices such as televisions and smartphones, have recently been recognized as emerging contaminants due to their widespread occurrence in the environment and potential negative impacts on human health. Airborne LCMs can undergo atmospheric oxidation reactions to form various transformation products. Despite the certainty of atmospheric transformation chemistry, the knowledge about the hazard properties of transformation products remains largely unknown. Here, we perform an in silico model-based evaluation of the persistence, bioaccumulation potential, mobility, and toxicity of two representative LCMs, namely, 1-ethyl-4-(4-(4-propylcyclohexyl)phenyl)benzene and 4''-ethyl-2'-fluoro-4-propyl-1,1':4',1''-terphenyl, and their transformation products. We found that, among the investigated transformation products, 38% have overall persistence greater than the minimum of 331 days among the persistent organic pollutants regulated by the Stockholm Convention, 62% meet the bioaccumulation threshold of 1000 L kg-1 used by the United States Environmental Protection Agency, 44% are classified "mobile" according to the criterion used by the German Environmental Agency, and 58% have the potential to induce unacceptable toxic effects in aquatic organisms. Furthermore, we identified several transformation products with increased persistence, bioaccumulation potential, and mobility compared to their parent compounds. These findings not only offer insights for prioritizing LCM transformation products for future risk assessment, but also underscore the significance of considering atmospheric transformation in the evaluation of environmental risks posed by emerging contaminants, including LCMs.
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Cristais Líquidos , Poluentes Químicos da Água , Humanos , Estados Unidos , Poluentes Químicos da Água/análise , OxirreduçãoRESUMO
The gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle. L. plantarum, L. ingluviei, L. salivarius, and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (MyHC SM and MyHC FRM), mitochondrial function (Tfam and CoxVa), and glucose metabolism (PFK, PK, PDH, IDH, and SDH), thereby increasing the fiber diameter and density. These three Lactobacillus species could be promising probiotics to improve the meat quality of chicken.IMPORTANCEThis study revealed that the L. plantarum, L. ingluviei, and L. salivarius could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.
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Galinhas , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Glucose , Lactobacillus , Animais , Galinhas/metabolismo , Galinhas/microbiologia , Glucose/metabolismo , Microbioma Gastrointestinal/fisiologia , Ácidos Graxos Voláteis/metabolismo , Lactobacillus/metabolismo , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Metabolismo Energético , Transplante de Microbiota FecalRESUMO
Sedimentary records of polycyclic aromatic hydrocarbons (PAHs) and phthalates could reflect energy consumption and industrial production adjustment. However, there is limited knowledge about their effects on variations of PAH and phthalate compositions in the sediment core. The PAH and phthalate sedimentary records in Huguangyan Maar Lake in Guangdong, China were constructed, and random forest models were adopted to quantify the associated impact factors. Sums of sixteen PAH (∑16 PAH) and seven phthalate (∑7 PAE) concentrations in the sediment ranged from 28.8 to 1110 and 246-4290 µg/kg dry weight in 1900-2020. Proportions of 5-6 ring PAHs to the ∑16 PAHs increased from 32.0 %-40.7 % in 1900-2020 with increased coal and petroleum consumption, especially after 1980. However, those of 2-3 ring PAHs decreased from 30.7 % to 23.6 % due to the biomass substitution with natural gas. The proportions of bis (2-ethylhexyl) phthalate to the ∑7 PAEs decreased from 52.3 %-29.1 % in 1900-2020, while those of di-isobutyl phthalate increased (13.7 % to 42.3 %). The shift from traditional plasticizers to non-phthalates drove this transformation, though the primary plastic production is increasing. Our findings underscore the effectiveness of optimizing energy structures and updating chemical products in reducing organic pollution in aquatic environments.
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Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Ácidos Ftálicos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , China , Sedimentos Geológicos/química , Lagos/química , Poluentes Químicos da Água/análise , Ácidos Ftálicos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Desenvolvimento EconômicoRESUMO
Prediction of blood cell flow is known as the difficult research by reason of the complexity of blood vessel. In this study, considering the complex structure of blood vessels, a mechanical model for red blood cell (RBC) based on unstructured grid has been established to study the flow characteristics of RBCs in complex blood vessels. In the model, the strain-energy function by Skalak is employed to model the shear elasticity and surface-area conservation of the membrane, and the hinge spring is used to describe the forces originating from local bending of the membrane. The immersed boundary method is utilized to couple the interphase force. Using the model, the stretching test of RBC is compared with the experiment data, and the good agreement verified the validation of the present model. The morphology of red blood cell and the blood viscosity in micro-vessel are studied. RBCs move with a symmetric shape (parachute shape) in small blood vessels, and the buckling instability is observed when the RBC flow slowly through a micro-vessel or a converging-diverging capillary. When the vessel diameter is around 10 µm, the reverse Fahraeus-Lindqvist effect is presented. The blood apparent viscosity shows linear increase with the blood hematocrit. In addition, Malaria infection can make the RBC deformability decreased and the blood apparent viscosity increased.
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Deformação Eritrocítica , Eritrócitos , Hematócrito , Hemodinâmica , CapilaresRESUMO
Aeriscardovia aeriphila, also known as Bifidobacterium aerophilum, was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin. Bifidobacterium species play important roles in preventing intestinal infections, decreasing cholesterol levels, and stimulating the immune system. In this study, we isolated a strain of bacteria from the duodenal contents of broiler chickens, which was identified as A. aeriphila, and then evaluated the effects of A. aeriphila on growth performance, antioxidant functions, immune functions, and gut microbiota in commercial broiler chickens. Chickens were orally gavaged with A. aeriphila (1×109 CFU/mL) for 21 d. The results showed that A. aeriphila treatment significantly increased the average daily gain and reduced the feed conversion ratio (P<0.001). The levels of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) were significantly increased following A. aeriphila treatment (P<0.05). Blood urea nitrogen and aspartate aminotransferase levels were decreased, whereas glucose and creatinine levels increased as a result of A. aeriphila treatment. Furthermore, the levels of serum antioxidant enzymes, including catalase (P<0.01), superoxide dismutase (P<0.001), and glutathione peroxidase (P<0.05), and total antioxidant capacity (P<0.05) were enhanced following A. aeriphila treatment. A. aeriphila treatment significantly increased the levels of serum immunoglobulin A (IgA) (P<0.05), IgG (P<0.01), IgM (P<0.05), interleukin-1 (IL-1) (P<0.05), IL-4 (P<0.05), and IL-10 (P<0.05). The broiler chickens in the A. aeriphila group had higher secretory IgA (SIgA) levels in the duodenum (P<0.01), jejunum (P<0.001), and cecum (P<0.001) than those in the control group. The messenger RNA (mRNA) relative expression levels of IL-10 (P<0.05) and IL-4 (P<0.001) in the intestinal mucosa of chickens were increased, while nuclear factor-|κB (NF|-|κB) (P<0.001) expression was decreased in the A. aeriphila group compared to the control group. Phylum-level analysis revealed Firmicutes as the main phylum, followed by Bacteroidetes, in both groups. The data also found that Phascolarctobacterium and Barnesiella were increased in A. aeriphila-treated group. In conclusion, oral administration of A. aeriphila could improve the growth performance, serum antioxidant capacity, immune modulation, and gut health of broilers. Our findings may provide important information for the application of A. aeriphila in poultry production.
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Aeriscardovia aeriphila, also known as Bifidobacterium aerophilum, was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin. Bifidobacterium species play important roles in preventing intestinal infections, decreasing cholesterol levels, and stimulating the immune system. In this study, we isolated a strain of bacteria from the duodenal contents of broiler chickens, which was identified as A. aeriphila, and then evaluated the effects of A. aeriphila on growth performance, antioxidant functions, immune functions, and gut microbiota in commercial broiler chickens. Chickens were orally gavaged with A. aeriphila (1×109 CFU/mL) for 21 d. The results showed that A. aeriphila treatment significantly increased the average daily gain and reduced the feed conversion ratio (P<0.001). The levels of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) were significantly increased following A. aeriphila treatment (P<0.05). Blood urea nitrogen and aspartate aminotransferase levels were decreased, whereas glucose and creatinine levels increased as a result of A. aeriphila treatment. Furthermore, the levels of serum antioxidant enzymes, including catalase (P<0.01), superoxide dismutase (P<0.001), and glutathione peroxidase (P<0.05), and total antioxidant capacity (P<0.05) were enhanced following A. aeriphila treatment. A. aeriphila treatment significantly increased the levels of serum immunoglobulin A (IgA) (P<0.05), IgG (P<0.01), IgM (P<0.05), interleukin-1 (IL-1) (P<0.05), IL-4 (P<0.05), and IL-10 (P<0.05). The broiler chickens in the A. aeriphila group had higher secretory IgA (SIgA) levels in the duodenum (P<0.01), jejunum (P<0.001), and cecum (P<0.001) than those in the control group. The messenger RNA (mRNA) relative expression levels of IL-10 (P<0.05) and IL-4 (P<0.001) in the intestinal mucosa of chickens were increased, while nuclear factor-|κB (NF|-|κB) (P<0.001) expression was decreased in the A. aeriphila group compared to the control group. Phylum-level analysis revealed Firmicutes as the main phylum, followed by Bacteroidetes, in both groups. The data also found that Phascolarctobacterium and Barnesiella were increased in A. aeriphila-treated group. In conclusion, oral administration of A. aeriphila could improve the growth performance, serum antioxidant capacity, immune modulation, and gut health of broilers. Our findings may provide important information for the application of A. aeriphila in poultry production.
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Antioxidantes , Microbioma Gastrointestinal , Animais , Suínos , Antioxidantes/farmacologia , Galinhas , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Interleucina-4/metabolismo , Interleucina-4/farmacologia , NF-kappa B/metabolismo , Imunidade , Dieta/veterinária , Ração Animal/análise , Suplementos Nutricionais/análiseRESUMO
BACKGROUND: The interaction between nutrition and immunity plays a vital role in nutrient digestion, absorption, and metabolism during poultry production. Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity. However, the mechanisms by which gut microbes regulate this process remain unclear. METHODS: We compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers (AA (lower mucosal immunity) and Chinese native Wuliang Mountain Black-bone chickens (WLMB) (higher mucosal immunity) using 16S rDNA sequencing, transcriptomic analysis, and immunoglobulin A (IgA) antibody repertoire sequencing. We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production. Next, we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity. Finally, we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells (IECs) using in vitro experiments. RESULTS: WLMB performs stronger mucosal immunity than AA, including higher IgA levels, more diverse IgA antibody repertoire, and higher bacterial affinity. Bacteroides was identified as the key microbes related to the intestinal IgA response. Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA, polymeric immunoglobin receptor (PIgR), B cell-activating factor of the TNF family (BAFF), and activation-induced cytidine deaminase (AID) in the duodenum. Additionally, Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines, including interleukin (IL)-10, IL-4, BAFF, and transforming growth factor-beta (TGF-ß), thus promoting IgA production in B cells by facilitating AID expression. CONCLUSION: Our study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers. Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing next-generation probiotics for broiler production.
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The native saltmarsh species Scirpus mariqueter (hereafter S. mariqueter) and the exotic species saltmarsh cordgrass (Spartina alterniflora Loisel., hereafter S. alterniflora), have been found commonly in regional saltmarsh ecosystems which received a large amount of sediment inputs from Yangtze River, eastern coasts of China. For the purpose of saltmarsh restoration and invasive species management, it is important to understand the response of vegetation species to various sediment inputs. This study investigated and compared the effects of sediment addition on S. mariqueter and S. alterniflora through laboratory experiment using vegetation samples collected from a natural saltmarsh with a high sedimentation rate (12 cm a-1). Plant growth parameters over their growth period, including survival rate, height and biomass were measured against sediment addition gradient (0 cm, 3 cm, 6 cm, 9 cm, and 12 cm in thickness). The results showed that sediment addition significantly affected the growth of vegetation but this effect varied between two species. Compared with the control group, the growth of S. mariqueter was promoted with sediment addition of 3-6 cm, but it turned to inhibition when the sediment thickness exceeded 6 cm. The growth of S. alterniflora was increased with increasing sediment addition till 9-12 cm, but the survival rate of each group kept stable. Overall, against a gradient sediment addition, S. mariqueter was found to benefit from low to moderate sediment addition (3-6 cm) but higher addition showed inhabitation effects. S. alterniflora benefited from increasing sediment addition to a point. When facing high sediment inputs, S. alterniflora was found to be more adaptable than S. mariqueter. These results have important implications for further studies on saltmarsh restoration and interspecific competition against a high sediment input background.
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Ecossistema , Áreas Alagadas , Poaceae , Biomassa , Rios , China , Espécies IntroduzidasRESUMO
Amyloid imaging has been widely used in Alzheimer's disease (AD) diagnosis and biomarker discovery through detecting the regional amyloid plaque density. It is essential to be normalized by a reference region to reduce noise and artifacts. To explore an optimal normalization strategy, we employ an automated machine learning (AutoML) pipeline, STREAMLINE, to conduct the AD diagnosis binary classification and perform permutation-based feature importance analysis with thirteen machine learning models. In this work, we perform a comparative study to evaluate the prediction performance and biomarker discovery capability of three amyloid imaging measures, including one original measure and two normalized measures using two reference regions (i.e., the whole cerebellum and the composite reference region). Our AutoML results indicate that the composite reference region normalization dataset yields a higher balanced accuracy, and identifies more AD-related regions based on the fractioned feature importance ranking.
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STREAMLINE is a simple, transparent, end-to-end automated machine learning (AutoML) pipeline for easily conducting rigorous machine learning (ML) modeling and analysis. The initial version is limited to binary classification. In this work, we extend STREAMLINE through implementing multiple regression-based ML models, including linear regression, elastic net, group lasso, and L21 norm. We demonstrate the effectiveness of the regression version of STREAMLINE by applying it to the prediction of Alzheimer's disease (AD) cognitive outcomes using multimodal brain imaging data. Our empirical results demonstrate the feasibility and effectiveness of the newly expanded STREAMLINE as an AutoML pipeline for evaluating AD regression models, and for discovering multimodal imaging biomarkers.
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OBJECTIVE: To examine the correlation between the plasma level of brain natriuretic peptide (BNP) and the hemodynamic parameters collected through Swan-Ganz flowing balloon catheter procedure in patients with noncardiac shock, in order to evaluate the potential for BNP to be used as prognostic indicator. METHODS: The plasma BNP and invasive hemodynamic parameters data [central venous pressure (CVP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), and cardiac output (CO)] were collected from 21 noncardiac shock patients received Swan-Ganz catheterization throughout a continuous surveillance for 3 days. The BNP, CVP, PAP, PCWP, CO in survivors (n = 8) and non-survivors (n = 13) were compared and the correlation between the value of BNP and the invasive hemodynamic parameters were analyzed using multiple regression. RESULTS: The mean value of BNP (ng/L) was significantly higher in non-survivors (708.06 ± 242.58 vs. 317.05 ± 140.21, P < 0.05). In day 1, no significant difference was found in any hemodynamic parameters between non-survivors and survivors. But in day 3, the non-survivors were found to have significantly higher CVP (mm Hg, 1 mm Hg = 0.133 kPa: 13.64 ± 4.00 vs. 9.92 ± 1.26, P < 0.05) and lower CO (L/min: 4.61 ± 2.06 vs. 6.95 ± 1.28, P < 0.05). The differences in PAP (mm Hg: 20.84 ± 8.48 vs. 16.82 ± 4.97) and PCWP (mm Hg: 13.60 ± 5.71 vs. 12.72 ± 4.98) remained insignificant (both P > 0.05) between the two groups. The correlation between BNP and the invasive hemodynamic parameters was modest there was no correlation between BNP and CVP, PAP, PCWP, CO (r = 0.157, 0.306, 0.229, -0.269, P = 0.16, 0.25, 0.09, 0.12). CONCLUSIONS: In patients with shock, both plasma BNP and invasive hemodynamic examination showed certain prognostic value. But in noncardiac shock cases, the increased BNP did not correlate with heart function, therefore it could not replace the Swan-Ganz catheter data to guide the treatment in these patients.