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1.
JMIR Res Protoc ; 13: e56484, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885500

RESUMO

BACKGROUND: Vascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients' quality of life. Previous studies have reported that disorders of serum iron metabolism and iron deposition in the brain can lead to inflammation, abnormal protein aggregation and degeneration, and massive neuronal apoptosis in the central nervous system, which in turn leads to a progressive decline in cognitive processes. Our previous clinical studies have found acupuncture to be a safe and effective intervention for treating VCI, but the specific mechanisms require further exploration. OBJECTIVE: The objective of the trial is to evaluate the clinical efficacy of Tongdu Xingshen acupuncture and to investigate whether it can improve VCI by regulating brain iron deposition and body iron metabolism. METHODS: In total, 42 patients with VCI and 21 healthy individuals will participate in this clinical trial. The 42 patients with VCI will be randomized into acupuncture and control groups, while the 21 healthy individuals will be in the healthy control group. Both the control and acupuncture groups will receive conventional medical treatment and cognitive rehabilitation training. In addition, the acupuncture group will receive electroacupuncture treatment with Tongdu Xingshen for 30 minutes each time, 6 times a week for 4 weeks. Meanwhile, the healthy control group will not receive any intervention. All 3 groups will undergo baseline assessments of brain iron deposition, serum iron metabolism, and neuropsychological tests after enrollment. The acupuncture and control groups will be evaluated again at the end of 4 weeks of treatment, as described earlier. By comparing neuropsychological test scores between groups, we will examine the efficacy of Tongdu Xingshen acupuncture in treating VCI. Additionally, we will test the correlations between neuropsychological test scores, brain iron deposition, and body iron metabolism indexes to explore the possible mechanisms of Tongdu Xingshen acupuncture in treating VCI. RESULTS: Participants are currently being recruited. The first participant was enrolled in June 2023, which marked the official start of the experiment. As of the submission of the paper, there were 23 participants. The recruitment process is expected to continue until June 2025, at which point the processing and analysis of data will begin. As of May 15, 2024, up to 30 people have been enrolled in this clinical trial. CONCLUSIONS: This study will provide data on the effects of Tongdu Xingshen acupuncture on cerebral iron deposition as well as somatic iron metabolism in patients with VCI. These results will help to prove whether Tongdu Xingshen acupuncture can improve VCI by regulating brain iron deposition and body iron metabolism, which will provide the clinical and theoretical basis for the wide application of acupuncture therapy in VCI rehabilitation. TRIAL REGISTRATION: China Clinical Registration Agency ChiCTR2300072188; https://tinyurl.com/5fcydtkv. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56484.


Assuntos
Terapia por Acupuntura , Encéfalo , Disfunção Cognitiva , Ferro , Humanos , Terapia por Acupuntura/métodos , Ferro/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto
2.
Nat Microbiol ; 9(7): 1873-1883, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38902374

RESUMO

Historically neglected by microbial ecologists, soil viruses are now thought to be critical to global biogeochemical cycles. However, our understanding of their global distribution, activities and interactions with the soil microbiome remains limited. Here we present the Global Soil Virus Atlas, a comprehensive dataset compiled from 2,953 previously sequenced soil metagenomes and composed of 616,935 uncultivated viral genomes and 38,508 unique viral operational taxonomic units. Rarefaction curves from the Global Soil Virus Atlas indicate that most soil viral diversity remains unexplored, further underscored by high spatial turnover and low rates of shared viral operational taxonomic units across samples. By examining genes associated with biogeochemical functions, we also demonstrate the viral potential to impact soil carbon and nutrient cycling. This study represents an extensive characterization of soil viral diversity and provides a foundation for developing testable hypotheses regarding the role of the virosphere in the soil microbiome and global biogeochemistry.


Assuntos
Biodiversidade , Genoma Viral , Metagenoma , Microbiota , Microbiologia do Solo , Solo , Vírus , Vírus/genética , Vírus/classificação , Vírus/isolamento & purificação , Solo/química , Genoma Viral/genética , Microbiota/genética , Carbono/metabolismo , Metagenômica , Filogenia , Viroma/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação
3.
mSystems ; 9(6): e0111223, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38722174

RESUMO

Despite the explosion of soil metagenomic data, we lack a synthesized understanding of patterns in the distribution and functions of soil microorganisms. These patterns are critical to predictions of soil microbiome responses to climate change and resulting feedbacks that regulate greenhouse gas release from soils. To address this gap, we assay 1,512 manually curated soil metagenomes using complementary annotation databases, read-based taxonomy, and machine learning to extract multidimensional genomic fingerprints of global soil microbiomes. Our objective is to uncover novel biogeographical patterns of soil microbiomes across environmental factors and ecological biomes with high molecular resolution. We reveal shifts in the potential for (i) microbial nutrient acquisition across pH gradients; (ii) stress-, transport-, and redox-based processes across changes in soil bulk density; and (iii) greenhouse gas emissions across biomes. We also use an unsupervised approach to reveal a collection of soils with distinct genomic signatures, characterized by coordinated changes in soil organic carbon, nitrogen, and cation exchange capacity and in bulk density and clay content that may ultimately reflect soil environments with high microbial activity. Genomic fingerprints for these soils highlight the importance of resource scavenging, plant-microbe interactions, fungi, and heterotrophic metabolisms. Across all analyses, we observed phylogenetic coherence in soil microbiomes-more closely related microorganisms tended to move congruently in response to soil factors. Collectively, the genomic fingerprints uncovered here present a basis for global patterns in the microbial mechanisms underlying soil biogeochemistry and help beget tractable microbial reaction networks for incorporation into process-based models of soil carbon and nutrient cycling.IMPORTANCEWe address a critical gap in our understanding of soil microorganisms and their functions, which have a profound impact on our environment. We analyzed 1,512 global soils with advanced analytics to create detailed genetic profiles (fingerprints) of soil microbiomes. Our work reveals novel patterns in how microorganisms are distributed across different soil environments. For instance, we discovered shifts in microbial potential to acquire nutrients in relation to soil acidity, as well as changes in stress responses and potential greenhouse gas emissions linked to soil structure. We also identified soils with putative high activity that had unique genomic characteristics surrounding resource acquisition, plant-microbe interactions, and fungal activity. Finally, we observed that closely related microorganisms tend to respond in similar ways to changes in their surroundings. Our work is a significant step toward comprehending the intricate world of soil microorganisms and its role in the global climate.


Assuntos
Metagenoma , Microbiota , Microbiologia do Solo , Microbiota/genética , Solo/química , Ecossistema , Metagenômica/métodos , Filogenia , Fungos/genética , Fungos/classificação , Bactérias/genética , Bactérias/classificação
4.
Nat Chem Biol ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302607

RESUMO

The leaf-cutter ant fungal garden ecosystem is a naturally evolved model system for efficient plant biomass degradation. Degradation processes mediated by the symbiotic fungus Leucoagaricus gongylophorus are difficult to characterize due to dynamic metabolisms and spatial complexity of the system. Herein, we performed microscale imaging across 12-µm-thick adjacent sections of Atta cephalotes fungal gardens and applied a metabolome-informed proteome imaging approach to map lignin degradation. This approach combines two spatial multiomics mass spectrometry modalities that enabled us to visualize colocalized metabolites and proteins across and through the fungal garden. Spatially profiled metabolites revealed an accumulation of lignin-related products, outlining morphologically unique lignin microhabitats. Metaproteomic analyses of these microhabitats revealed carbohydrate-degrading enzymes, indicating a prominent fungal role in lignocellulose decomposition. Integration of metabolome-informed proteome imaging data provides a comprehensive view of underlying biological pathways to inform our understanding of metabolic fungal pathways in plant matter degradation within the micrometer-scale environment.

5.
J Cell Mol Med ; 28(1): e18023, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38146147

RESUMO

In recent years, an increasing number of observational studies have revealed an association between gut microbiota composition and psoriasis patients. However, whether this association reflects a causal relationship remains unclear. This study aimed to identify the causal relationship between gut microbiota and psoriasis through relevant research. In order to determine whether gut microbiota and psoriasis are causally related, we conducted a Mendelian randomization analysis using summary statistics from genome-wide association studies (GWAS). As the exposure factor, we used summary statistics data from a GWAS study conducted by the MiBioGen Consortium, including 18,340 individuals with whole-genome gut microbiota composition, and data from the FinnGen GWAS study on psoriasis, including 9267 patients and 364,071 controls as the disease outcome. Two-sample Mendelian randomization analysis was subsequently performed with inverse variance weighted, MR-Egger and weighted median, while sensitivity analyses were conducted to address heterogeneity and horizontal pleiotropy. The IVW results confirmed the causal relationship between certain gut microbiota groups and psoriasis. Specifically, family Veillonellaceae (OR = 1.162, 95% CI: 1.038-1.301, p = 0.009), genus Candidatus Soleaferrea (OR = 1.123, 95% CI: 1.011-1.247, p = 0.030) and genus Eubacterium fissicatena group (OR = 0.831, 95% CI: 0.755-0.915, p = 0.00016) showed significant associations. Sensitivity analysis did not reveal any abnormalities in SNPs. Currently, we have found some causal relationship between the gut microbiota and psoriasis. However, the study needs further RCTs for further validation.


Assuntos
Microbioma Gastrointestinal , Psoríase , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
6.
Neuropsychiatr Dis Treat ; 19: 2657-2671, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077236

RESUMO

Background: Post-stroke depression (PSD) is one of the most common complications of stroke. Electroacupuncture (EA) is an effective traditional Chinese medicine treatment for PSD, which is widely used in clinical settings. EA has a significant therapeutic effect against PSD, but the mechanism is still unclear. This study aimed to determine whether EA ameliorates depression-like behaviors in PSD rats by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated mitochondrial function. Methods: Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) were used to develop a PSD rat model. To elucidate the role of AMPK in EA treatment, compound C, a selective inhibitor of AMPK, was injected into the lateral ventricle of rats before EA treatment. EA treatment was performed for 14 consecutive days for 30 min per day after PSD modeling. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. Behavioral tests were conducted to evaluate depression-like phenotypes in rats. Depression-like behaviors were tested by sucrose preference test (SPT), novelty suppressed feeding test (NSFT), and open-field test (OFT). The structure and morphology of the prefrontal cortex were observed by histopathological hematoxylin-eosin (HE) and Nissl staining. The mitochondrial morphology and function were analyzed by colorimetry, chemiluminescence, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: EA treatment successfully ameliorated depression-like behaviors, upregulated AMPK expression, and improved mitochondrial function. However, AMPK inhibition by Compound C exacerbated depression-like behaviors and aggravated neuronal and mitochondrial injury in PSD rats. Conclusion: EA treatment improved depression-like behaviors in PSD rats and promoted mitochondrial function by activating AMPK.

7.
Sci Rep ; 13(1): 22543, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110541

RESUMO

Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised a two-sample Mendelian randomisation (MR) study to evaluate the potential causal association between 486 blood metabolites and SLE. Exposure data at the metabolite level were extracted from 7824 European Genome-wide association studies (GWAS). Preliminary analysis utilised SLE GWAS data from FinnGen. The primary method for causal analysis relied on random inverse variance weighting (IVW). To ensure robustness, sensitivity analyses included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Steiger testing and linkage disequilibrium score regression were employed to validate the identified metabolites. This study identified 12 metabolites, comprising six known chemical structures: 1,5-anhydroglucitol(1,5-AG) [odds ratio (OR) = 0.100, 95% confidence interval (CI): 0.015-0.773, P = 0.027), gamma-glutamylthreonine (OR = 0.077, 95% CI: 0.010-0.574, P = 0.012), 5-dodecenoate(12:1n7) (OR = 0.205, 95% CI: 0.061-0.685, P = 0.010), linoleoylglycerophosphoethanolamine * (OR = 0.159, 95% CI: 0.027-0.933, P = 0.044), erythrose (OR = 88.331,95% CI:1.098-63.214, P = 0.040) and 1-, adrenate (22:4n6) (OR = 9.876, 95% CI: 1.753-55.639, P = 0.001)]. Additionally, we found associations between SLE and six unknown chemical structures: X-06351 (OR = 0.071, 95% CI: 0.006-0.817, P = 0.034), X-10810 (OR = 4.268 95% CI: 1.260-14.459, P = 0.020), X-11412 (OR = 5.418 95% CI: 1.068-27.487, P = 0.041), X-11905 (OR = 0.551, 95%CI: 0.304-0.997, P = 0.049), X-12038 (OR = 0.178 95%CI: 0.032-0.988, P = 0.045), X-12217 (OR = 0.174 95%CI: 0.044-0.680, P = 0.014). This study offers evidence supporting a causal relationship between SLE and 12 circulating metabolites, six of which have known chemical structures and six that remain unidentified. These findings introduce a new perspective for further exploration of SLE mechanisms.


Assuntos
Estudo de Associação Genômica Ampla , Lúpus Eritematoso Sistêmico , Humanos , Análise da Randomização Mendeliana , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/genética , Nonoxinol
9.
Nat Commun ; 14(1): 7666, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996432

RESUMO

Bacteriophages are abundant in soils. However, the majority are uncharacterized, and their hosts are unknown. Here, we apply high-throughput chromosome conformation capture (Hi-C) to directly capture phage-host relationships. Some hosts have high centralities in bacterial community co-occurrence networks, suggesting phage infections have an important impact on the soil bacterial community interactions. We observe increased average viral copies per host (VPH) and decreased viral transcriptional activity following a two-week soil-drying incubation, indicating an increase in lysogenic infections. Soil drying also alters the observed phage host range. A significant negative correlation between VPH and host abundance prior to drying indicates more lytic infections result in more host death and inversely influence host abundance. This study provides empirical evidence of phage-mediated bacterial population dynamics in soil by directly capturing specific phage-host interactions.


Assuntos
Bacteriófagos , Bacteriófagos/genética , Metagenoma , Solo , Bactérias/genética , Lisogenia/genética
10.
Front Pharmacol ; 14: 984794, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731741

RESUMO

Background: The Pilot Plan of National Centralized Volume-Based Procurement (NCVBP) was adopted to cope with the rapid increase in drug expenditures. This research aimed to quantitatively evaluate the impact of the NCVBP on antiviral medications for the hepatitis B virus. Methods: Data on nucleoside analogs (NAs) medications of hepatitis B virus monthly procurement records in the pilot cities from January 2018 to December 2019 were extracted from the China Drug Supply Information Platform (CDSIP). The impacts of the NCVBP on purchased volumes, expenditures, and pre-defined daily dose costs were evaluated by interrupted time-series (ITS) analysis using Stata 16.0. We constructed two segments with one interruptive point (March 2019). Results: Compared to the same period between pre-and post-intervention, the purchased volume of NAs medications were increased by 92.85%, and selected medications were increased by 119.09%. Analysis of changes in the level of NAs medication followed a decrease in purchased expenditure (coefficient: 5364.88, p < 0.001), meanwhile, the purchased volume was increased with statistical significance (coefficient:605.49, p < 0.001). The Defined Daily Dose cost (DDDc) of NAs medication followed a decrease (coefficient: 8.90, p < 0.001). The NCVBP reform was followed by an increase of 618.41 ten thousand Defined Daily Dose (DDD) (p < 0.001) in purchased volume and a reduction of 5273.84 ten thousand Chinese Yuan (CNY) (p < 0.001) in the purchased expenditure of selected medications in the level. The DDDc of selected medications decreased in the level (coefficient: 9.87, p < 0.001), while the DDDc of alternative medications increased in the slope (coefficient:0.07, p = 0.030). The purchased volume and expenditure of bid-winning products increased by 964.08 ten thousand DDD and 637.36 ten thousand CNY in the level (p < 0.001). An increase of 633.46 ten thousand DDD (p < 0.001) in purchased volume and a reduction of 4285.32 ten thousand CNY (p < 0.001) in the purchased expenditure of generic drugs in the level was observed. Conclusion: The NCVBP reduced the DDDc of NAs medication, improved the utilization of the selected medications, and promoted the usage of generic products.

11.
Anal Chem ; 95(33): 12313-12320, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37565815

RESUMO

The detection of formic acid vapor in the usage environment is extremely important for human health and safety. The utilization of metal-organic frameworks (MOFs) for the detection of gaseous molecules is an attractive strategy. However, the rational design and construction of MOF-based gas sensors with high sensitivity and mechanical stability remain a significant challenge. In this study, a simple approach is reported to fabricate colorimetric aerogel sensors assembled from MOF particles via ice template-assisted methods. As the aerogel sensor with staggered lamellae structures significantly provides a high air-volume intake of flowing gas, it generates a sufficient probability of contact reactions for highly mobile target molecules. Additionally, it enhances the mechanical stability by providing stress resistance between the staggered lamellae structures. Compared to conventional film sensors for the detection of formic acid molecules, aerogel sensors exhibit an 8-fold lower limit of detection, 15-fold better sensitivity at low concentrations, 34-fold faster response time, and higher stability. This approach shows great potential for rapid and real-time detection of target molecules as well as superior performance in the structural construction of various gas-sensitive materials.

12.
Nat Rev Microbiol ; 21(5): 296-311, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36352025

RESUMO

Soil viruses are highly abundant and have important roles in the regulation of host dynamics and soil ecology. Climate change is resulting in unprecedented changes to soil ecosystems and the life forms that reside there, including viruses. In this Review, we explore our current understanding of soil viral diversity and ecology, and we discuss how climate change (such as extended and extreme drought events or more flooding and altered precipitation patterns) is influencing soil viruses. Finally, we provide our perspective on future research needs to better understand how climate change will impact soil viral ecology.


Assuntos
Ecossistema , Vírus , Solo , Mudança Climática , Ecologia , Microbiologia do Solo
13.
mSystems ; 7(6): e0058222, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36453933

RESUMO

Arctic permafrost is thawing due to global warming, with unknown consequences on the microbial inhabitants or associated viruses. DNA viruses have previously been shown to be abundant and active in thawing permafrost, but little is known about RNA viruses in these systems. To address this knowledge gap, we assessed the composition of RNA viruses in thawed permafrost samples that were incubated for 97 days at 4°C to simulate thaw conditions. A diverse RNA viral community was assembled from metatranscriptome data including double-stranded RNA viruses, dominated by Reoviridae and Hypoviridae, and negative and positive single-stranded RNA viruses, with relatively high representations of Rhabdoviridae and Leviviridae, respectively. Sequences corresponding to potential plant and human pathogens were also detected. The detected RNA viruses primarily targeted dominant eukaryotic taxa in the samples (e.g., fungi, Metazoa and Viridiplantae) and the viral community structures were significantly associated with predicted host populations. These results indicate that RNA viruses are linked to eukaryotic host dynamics. Several of the RNA viral sequences contained auxiliary metabolic genes encoding proteins involved in carbon utilization (e.g., polygalacturosase), implying their potential roles in carbon cycling in thawed permafrost. IMPORTANCE Permafrost is thawing at a rapid pace in the Arctic with largely unknown consequences on ecological processes that are fundamental to Arctic ecosystems. This is the first study to determine the composition of RNA viruses in thawed permafrost. Other recent studies have characterized DNA viruses in thawing permafrost, but the majority of DNA viruses are bacteriophages that target bacterial hosts. By contrast RNA viruses primarily target eukaryotic hosts and thus represent potential pathogenic threats to humans, animals, and plants. Here, we find that RNA viruses in permafrost are novel and distinct from those in other habitats studied to date. The COVID-19 pandemic has heightened awareness of the importance of potential environmental reservoirs of emerging RNA viral pathogens. We demonstrate that some potential pathogens were detected after an experimental thawing regime. These results are important for understanding critical viral-host interactions and provide a better understanding of the ecological roles that RNA viruses play as permafrost thaws.


Assuntos
COVID-19 , Pergelissolo , Vírus de RNA , Humanos , Pergelissolo/química , Solo/química , Ecossistema , Eucariotos/metabolismo , Pandemias , Vírus de RNA/genética , Plantas/metabolismo , Carbono/metabolismo
14.
Front Public Health ; 10: 989625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249207

RESUMO

Objectives: Promoting equity in healthcare resource allocation (EHRA) has become a critical political agenda of governments at all levels since the ambitious Universal Health Coverage was launched in China in 2009, while the role of an important institutional variable-fiscal autonomy of subnational governments-is often overlooked. The present study was designed to determine the effect of FASG on EHRA and its potential mechanism of action and heterogeneity characteristics to provide empirical support for the research field expansion and relative policies making of EHRA. Methods: From the start, we utilized the Theil index and the entropy method to calculate the EHRA index of 22 provinces (2011-2020) based on the medical resource data of 287 prefecture-level cities. Furthermore, we used the two-way fixed effects model (FE) to identify and analyze the impact of FASG on EHRA and then used three robustness test strategies and two-stage least squares (2SLS) regression to verify the reliability of the conclusions and deal with potential endogeneity problems, respectively. At last, we extend the baseline regression model and obtain the two-way FE threshold model for conducting heterogeneity analysis, which makes us verify whether the baseline model has nonlinear characteristics. Results: The static value and the trend of interannual changes in the EHRA values in different provinces are both very different. The regression results of the two-way FE model show that FASG has a significant positive impact on EHRA, and the corresponding estimated coefficient is - 0.0849 (P < 0.01). Moreover, this promotion effect can be reflected through two channels: enhancing the intensity of government health expenditure (IGHE) and optimizing the allocation of human resources for health (AHRH). At last, under the different economic and demographic constraints, the impact of FASG on EHRA has nonlinear characteristics, i.e., after crossing a specific threshold of per capita DGP (PGDP) and population density (PD), the promotion effect is reduced until it is not statistically significant, while after crossing a particular threshold of dependency ratio (DR), the promotion effect is further strengthened and still statistically significant. Conclusions: FASG plays an essential role in promoting EHRA, which shows that subnational governments need to attach great importance to the construction of fiscal capability in the allocation of health care resources, effectively improve the equity of medical and health fiscal expenditures, and promote the sustainable improvement of the level of EHRA.


Assuntos
Governo , Alocação de Recursos , China , Gastos em Saúde , Humanos , Reprodutibilidade dos Testes
15.
Nat Commun ; 13(1): 5485, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123347

RESUMO

Metagenomics is unearthing the previously hidden world of soil viruses. Many soil viral sequences in metagenomes contain putative auxiliary metabolic genes (AMGs) that are not associated with viral replication. Here, we establish that AMGs on soil viruses actually produce functional, active proteins. We focus on AMGs that potentially encode chitosanase enzymes that metabolize chitin - a common carbon polymer. We express and functionally screen several chitosanase genes identified from environmental metagenomes. One expressed protein showing endo-chitosanase activity (V-Csn) is crystalized and structurally characterized at ultra-high resolution, thus representing the structure of a soil viral AMG product. This structure provides details about the active site, and together with structure models determined using AlphaFold, facilitates understanding of substrate specificity and enzyme mechanism. Our findings support the hypothesis that soil viruses contribute auxiliary functions to their hosts.


Assuntos
Solo , Vírus , Carbono , Quitina , Glicosídeo Hidrolases/metabolismo , Proteínas Virais/genética , Vírus/genética
16.
J Proteome Res ; 21(8): 2023-2035, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35793793

RESUMO

Metaproteomics has been increasingly utilized for high-throughput characterization of proteins in complex environments and has been demonstrated to provide insights into microbial composition and functional roles. However, significant challenges remain in metaproteomic data analysis, including creation of a sample-specific protein sequence database. A well-matched database is a requirement for successful metaproteomics analysis, and the accuracy and sensitivity of PSM identification algorithms suffer when the database is incomplete or contains extraneous sequences. When matched DNA sequencing data of the sample is unavailable or incomplete, creating the proteome database that accurately represents the organisms in the sample is a challenge. Here, we leverage a de novo peptide sequencing approach to identify the sample composition directly from metaproteomic data. First, we created a deep learning model, Kaiko, to predict the peptide sequences from mass spectrometry data and trained it on 5 million peptide-spectrum matches from 55 phylogenetically diverse bacteria. After training, Kaiko successfully identified organisms from soil isolates and synthetic communities directly from proteomics data. Finally, we created a pipeline for metaproteome database generation using Kaiko. We tested the pipeline on native soils collected in Kansas, showing that the de novo sequencing model can be employed as an alternative and complementary method to construct the sample-specific protein database instead of relying on (un)matched metagenomes. Our pipeline identified all highly abundant taxa from 16S rRNA sequencing of the soil samples and uncovered several additional species which were strongly represented only in proteomic data.


Assuntos
Microbiota , Proteômica , Microbiota/genética , Peptídeos/análise , Peptídeos/genética , Proteoma/genética , Proteômica/métodos , RNA Ribossômico 16S/genética , Solo
17.
Front Pharmacol ; 13: 813213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237164

RESUMO

Background: The overuse of antibiotics is a serious public health problem and a major challenge in China, and China lacks up-to-date evidence on the nationwide antibiotic use in different healthcare settings. The changes of China's antibiotic use under the COVID-19 pandemic are still unknown. Objective: This study aimed to investigate the use of antibiotics in China's public medical institutions based on a three-year nationwide surveillance and to examine the impact of the COVID-19 pandemic on China's antibiotic consumption. Methods: This study used nationwide drug procurement data from the China Drug Supply Information Platform (CDSIP). We retrospectively analyzed antibiotic procurement data of 9,176 hospitals and 39,029 primary healthcare centers (PHCs) from 31 provinces in mainland China from January 2018 to December 2020. Antibiotic utilization was measured by defined daily doses (DDDs) and DDD per 1,000 inhabitants per day (DID). Generalized linear regression models were established to quantify the impact of the COVID-19 pandemic on antibiotic use. Results: The total antibiotic consumption among all healthcare settings increased from 12.94 DID in 2018 to 14.45 DID in 2019, and then dropped to 10.51 DID in 2020. More than half of antibiotics were consumed in PHCs, especially in central regions (59%-68%). The use of penicillins (J01C) and cephalosporins (J01D) accounted for 32.02% and 28.86% of total antibiotic consumption in 2020. During 2018-2020, parenteral antibiotics accounted for 31%-36% of total antibiotic consumption; the proportion is more prominent in central and western regions and the setting of hospitals. Access category antibiotics comprised 40%-42% of the total utilization. Affected by COVID-19, the antibiotic consumption was significantly dropped both in hospitals (ß = -.11, p < .001) and PHCs (ß = -.17, p < .001), as well as in total (ß = -.14, p < .001). Significant increments were observed in the proportion of total antibiotics (ß = .02, p = .024) consumed in hospitals (against the consumption in all healthcare settings), as well as parenteral antibiotics (ß = 1.73, p = .001). Conclusion: The consistent preferred use of penicillin and cephalosporin, as well as injections, among China's public healthcare institutions should draw concern. China's antibiotic consumption significantly declined during the COVID-19 pandemic, which brings opportunities for antibiotic use management in China.

18.
J Mater Chem B ; 10(14): 2471-2480, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-34820680

RESUMO

Filtration membranes are widely applied in medical fields. However, these membranes are challenged by bacterial contamination in hospitals, which increases the risk of nosocomial infections. Thus, it is significant to develop antibacterial filtration membranes. In this work, an oxidated dextran (ODex)-based antibacterial coating was designed and constructed on microfiltration (MF) membranes and melt-blown fabrics. Polyhexamethylene guanidine (PHMG) was synthesized as an antibacterial agent, and was fixed by ODex onto filtration membranes. The functionalized MF membranes increased the filtration efficiency for E. coli from 20.9% to 99.9%, and improved the absorption ratio for endotoxin by 59.1%, while the water flow rate still remained as high as 5255 L (h m2)-1. Furthermore, the trapped bacteria were inactivated by the antibacterial coating. For the melt-blown fabrics, the aerosol filtration efficiency was increased from 74.6% to 81.0%, and the antibacterial efficiency was promoted to 92.0%. The present work developed a facile and universal antibacterial functionalization strategy for filtration membranes, which provided a new method for the design and development of various novel antibacterial filtration materials in the medical field.


Assuntos
Antibacterianos , Escherichia coli , Antibacterianos/farmacologia , Filtração/métodos , Polissacarídeos , Têxteis
19.
mBio ; 12(6): e0259521, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34724822

RESUMO

Soil viruses are abundant, but the influence of the environment and climate on soil viruses remains poorly understood. Here, we addressed this gap by comparing the diversity, abundance, lifestyle, and metabolic potential of DNA viruses in three grassland soils with historical differences in average annual precipitation, low in eastern Washington (WA), high in Iowa (IA), and intermediate in Kansas (KS). Bioinformatics analyses were applied to identify a total of 2,631 viral contigs, including 14 complete viral genomes from three deep metagenomes (1 terabase [Tb] each) that were sequenced from bulk soil DNA. An additional three replicate metagenomes (∼0.5 Tb each) were obtained from each location for statistical comparisons. Identified viruses were primarily bacteriophages targeting dominant bacterial taxa. Both viral and host diversity were higher in soil with lower precipitation. Viral abundance was also significantly higher in the arid WA location than in IA and KS. More lysogenic markers and fewer clustered regularly interspaced short palindromic repeats (CRISPR) spacer hits were found in WA, reflecting more lysogeny in historically drier soil. More putative auxiliary metabolic genes (AMGs) were also detected in WA than in the historically wetter locations. The AMGs occurring in 18 pathways could potentially contribute to carbon metabolism and energy acquisition in their hosts. Structural equation modeling (SEM) suggested that historical precipitation influenced viral life cycle and selection of AMGs. The observed and predicted relationships between soil viruses and various biotic and abiotic variables have value for predicting viral responses to environmental change. IMPORTANCE Soil viruses are abundant but poorly understood. Because soil viruses regulate the dynamics of their hosts and potentially key processes in soil ecology, it is important to understand them better. Here, we leveraged massive DNA sequencing to unearth previously unknown soil viruses. We found that soil viruses differed across a historical gradient of precipitation. We compared soil viruses from Iowa, which is traditionally wetter, to those from Washington, which is traditionally drier, and from Kansas, which is intermediate. This study provides strong evidence that changes in historical precipitation impact not only the types of soil viruses but also their functional potential.


Assuntos
Vírus de DNA , Pradaria , Microbiologia do Solo , Bactérias/virologia , Bacteriófagos , Biologia Computacional , Vírus de DNA/genética , Ecossistema , Genoma Viral , Lisogenia , Metagenoma , Metagenômica , Análise de Sequência de DNA , Solo , Washington
20.
Commun Biol ; 4(1): 992, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446837

RESUMO

Soil is known to harbor viruses, but the majority are uncharacterized and their responses to environmental changes are unknown. Here, we used a multi-omics approach (metagenomics, metatranscriptomics and metaproteomics) to detect active DNA viruses and RNA viruses in a native prairie soil and to determine their responses to extremes in soil moisture. The majority of transcribed DNA viruses were bacteriophage, but some were assigned to eukaryotic hosts, mainly insects. We also demonstrated that higher soil moisture increased transcription of a subset of DNA viruses. Metaproteome data validated that the specific viral transcripts were translated into proteins, including chaperonins known to be essential for virion replication and assembly. The soil viral chaperonins were phylogenetically distinct from previously described marine viral chaperonins. The soil also had a high abundance of RNA viruses, with highest representation of Reoviridae. Leviviridae were the most diverse RNA viruses in the samples, with higher amounts in wet soil. This study demonstrates that extreme shifts in soil moisture have dramatic impacts on the composition, activity and potential functions of both DNA and RNA soil viruses.


Assuntos
Vírus de DNA/isolamento & purificação , Metagenoma , Vírus de RNA/isolamento & purificação , Microbiologia do Solo , Solo/química , Kansas , Metagenômica , Proteoma , Transcriptoma
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