Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 483
Filtrar
1.
JCI Insight ; 7(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35938531

RESUMO

Genetic polymorphisms are associated with the development of nonalcoholic fatty liver disease (NAFLD). Semaphorin7a (Sema7a) deficiency in mouse peritoneal macrophages reduces fatty acid (FA) oxidation. Here, we identified 17 individuals with SEMA7A heterozygous mutations in 470 patients with biopsy-proven NAFLD. SEMA7A heterozygous mutations increased susceptibility to NAFLD, steatosis severity, and NAFLD activity scores in humans and mice. The Sema7aR145W mutation (equivalent to human SEMA7AR148W) significantly induced small lipid droplet accumulation in mouse livers compared with WT mouse livers. Mechanistically, the Sema7aR145W mutation increased N-glycosylated Sema7a and its receptor integrin ß1 proteins in the cell membranes of hepatocytes. Furthermore, Sema7aR145W mutation enhanced its protein interaction with integrin ß1 and PKC-α and increased PKC-α phosphorylation, which were both abrogated by integrin ß1 silencing. Induction of PKCα_WT, but not PKCα_dominant negative, overexpression induced transcriptional factors Srebp1, Chrebp, and Lxr expression and their downstream Acc1, Fasn, and Cd36 expression in primary mouse hepatocytes. Collectively, our findings demonstrate that the SEMA7AR148W mutation is a potentially new strong genetic determinant of NAFLD and promotes intrahepatic lipid accumulation and NAFLD in mice by enhancing PKC-α-stimulated FA and triglyceride synthesis and FA uptake. The inhibition of hepatic PKC-α signaling may lead to novel NAFLD therapies.

2.
Appl Environ Microbiol ; : e0104222, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35938788

RESUMO

A large amount of long-chain fatty acids (LCFA) are generated after lipids hydrolysis in anaerobic digestion (AD), and LCFA are difficult to be biodegraded. This study showed that hydrochar (HC), which was produced during the hydrothermal liquefaction of organic wastes, significantly increased the methane production rate (by 56.9%) of oleate, a typical refractory model LCFA. Genomic-centric metatranscriptomics analysis revealed that three novel microbes (Bin138 Spirochaetota sp., Bin35 Smithellaceae sp., and Bin54 Desulfomonilia sp.) that were capable of degrading LCFA were enriched by HC, which played an important role in the degradation of oleate. LCFA was degraded to acetate through the well-known LCFA ß-oxidation pathway and the combined ß-oxidation and butyrate oxidation pathway. In addition, it was found that HC promoted the direct interspecies electron transfer (DIET) between Methanothrix sp. and Bin54 Desulfomonilia sp. The enriched new types of LCFA-degrading bacteria and the promotion of DIET contributed to the improved methane production rate of oleate by HC. IMPORTANCE Long-chain fatty acids (LCFA) are difficult to be degraded in anaerobic digestion (AD), and the known LCFA degrading bacteria are only limited to the families Syntrophomonadaceae and Syntrophaceae. Here, we found that hydrochar effectively promoted AD of LCFA, and the new LCFA-degrading bacteria and a new metabolic pathway were also revealed based on genomic-centric metatranscriptomic analysis. This study provided a new method for enhancing the AD of organic wastes with high content of LCFA and increased the understanding of the microbes and their metabolic pathways involved in AD of LCFA.

3.
Front Neurol ; 13: 854226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911924

RESUMO

Background: For patients with symptomatic intracranial and vertebral artery stenosis who receive endovascular treatment, in-stent restenosis (ISR) is associated with the recurrence of ischemic stroke. This study evaluated a drug-eluting stent (DES) vs. bare metal stent (BMS) for the treatment of symptomatic intracranial and vertebral artery stenosis. Methods: The trial was a multicenter, 1:1 randomized, prospective feasibility clinical trial with 10 participating centers in China from March 2014 to October 2015. Eligible patients had symptomatic intracranial and vertebral artery stenosis (70%-99%) and had medical drug treatment failure. The primary endpoint was the rate of in-stent restenosis at 180 days of randomization. The secondary endpoint was a composite of the following two outcomes: (1) ischemic stroke or transient cerebral ischemia (TIA) in the same territory as the presenting event (distal to the target lesion) between 30 days and 1 year after randomization and (2) successful stent implantation. The safety outcome was the presence of stroke in any territory and death within 30 days of randomization or adverse events. Group t-tests or Wilcoxon rank-sum tests were used for the intergroup comparison of quantitative data according to the data distribution. The chi-square test or exact probability method was used for the classification data. The Wilcoxon rank-sum test or CMH test was used for the categorical data. Results: We enrolled 188 patients at 10 medical centers in China (92 assigned to the DES group and 96 to the BMS group). The mean age of the 188 study participants was 61.6 years (range, 38-75 years); 152 participants (80.9%) were male. There were 28 patients (43.8%) with an ISR at 180 days in the BMS group and 10 patients (14.5%) in the DES group [risk difference, 29.3% (95% CI, 14.5%-44.0%); P = 0.001]. The percent of patients with ischemic stroke or TIA in the same territory between 30 days and 1 year was 5.2% (5/96) in the BMS group and 2.2% (2/92) in the DES group [risk difference, 3.0%; (95% CI, -2.3% to 8.2%); P = 0.354]. The percent of patients with successful stent implantation was 99.0% (95/96) in the BMS group and 97.8% (90/92) in the DES group [risk difference, 1.1%; (95% CI, -1.7% to 3.9%); P = 0.584]. In total, five patients (5.2%) in the BMS group and three patients (3.3%) in the DES group [risk difference, 1.9%; (95% CI, -2.3% to 6.1%); P = 0.721] had stroke in any territory and death within the 30-day follow-up. Total adverse events occurred 167 times in 72 patients (75.0%) in the BMS group compared with 114 times in 59 patients (64.1%) in the DES group [risk difference, 10.9%; (95% CI, -0.1% to 21.7%); P = 0.115]. Conclusions: Among patients with symptomatic intracranial arterial stenosis and vertebral artery stenosis, the use of a drug-eluting stent compared with a bare metal stent resulted in a decreased risk of ISR, similar successful stent implantation, and similar adverse events. These findings support the use of a drug-eluting stent for patients with symptomatic intracranial arterial stenosis and vertebral artery stenosis. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=148272, identifier: ChiCTR2200055925.

4.
Sci Rep ; 12(1): 13309, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922642

RESUMO

As a highly infectious epidemic in aquaculture, Pseudomonas plecoglossicida infection results in high mortality of teleosts and serious economic losses. Host-pathogen interactions shape the outcome of an infection, yet we still understand little about the molecular mechanism of these pathogen-mediated processes. Here, a P. plecoglossicida strain (NZBD9) and Epinephelus coioides were investigated as a model system to characterize pathogen-induced host metabolic remodeling over the course of infection. We present a non-targeted metabolomics profiling of E. coioides spleens from uninfected E. coioides and those infected with wild-type and clpV-RNA interference (RNAi) strains. The most significant changes of E. coioides upon infection were associated with amino acids, lysophospatidylcholines, and unsaturated fatty acids, involving disturbances in host nutritional utilization and immune responses. Dihydrosphingosine and fatty acid 16:2 were screened as potential biomarkers for assessing P. plecoglossicida infection. The silencing of the P. plecoglossicida clpV gene significantly recovered the lipid metabolism of infected E. coioides. This comprehensive metabolomics study provides novel insights into how P. plecoglossicida shape host metabolism to support their survival and replication and highlights the potential of the virulence gene clpV in the treatment of P. plecoglossicida infection in aquaculture.


Assuntos
Bass , Doenças dos Peixes , Infecções por Pseudomonas , Animais , Proteínas de Bactérias/metabolismo , Bass/genética , Doenças dos Peixes/genética , Pseudomonas/fisiologia , Infecções por Pseudomonas/genética
5.
Bioresour Technol ; : 127730, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35932944

RESUMO

Bio-utilization of lignocellulosic biomass is of huge significance as it can directly replace petroleum resources by producing liquid fuels and organic chemical products in a more sustainable way. However, studies on developing lignin-degrading microbial resources are still very few, which affects on establishing a consolidated bioprocessing of lignocellulosic resource. The main aim of this work is to discover thermostable laccases for lignin thermo-biodegradation by metagenome-mining and biochemical characterization. Results indicate that 124 putative thermostable laccase genes were identified from generated metagenomes. Significantly, 3 rationally selected proteins showed actual activity and structural stability at temperatures up to 60°C and pH values as low as 4.87. These active recombinant enzymes verify a practical advance in the functional prediction of target proteins, and simultaneous sequence-to-function relationships in this metagenome. In short, the identified thermostable laccase genes in this work could expand range of lignin biocatalysts and contribute to build an efficient lignin biorefinery.

6.
Front Pharmacol ; 13: 914518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784743

RESUMO

Background: Myocardial hypertrophy is a complex pathological process, which is a common manifestation during the development of various cardiovascular diseases. Hirudin has been shown to have therapeutic effects on a variety of cardiovascular diseases, however, its therapeutic effect on myocardial hypertrophy is still unknown, and its chemical and pharmacological characteristics remain to be elucidated. Methods: In this study, the network pharmacology method was used to characterize the mechanism of hirudin on myocardial hypertrophy. The potential protein targets of hirudin and myocardial hypertrophy were both obtained from the Genecards database, and potential pathways associated with genes were identified by Gene Ontology and pathway enrichment analysis, and the data were displayed in a visual manner. Subsequently, the potential mechanism of action of hirudin on myocardial hypertrophy predicted by network pharmacology analysis was verified by molecular docking, and finally, the main findings were further verified by in vitro experiments by molecular biology techniques. Based on the results obtained from the study of H9c2 cell line, the inhibitory effect of hirudin on myocardial hypertrophy was further proved in the primary rat cardiomyocytes. Results: A total of 250 targets of hirudin, and 5,376 targets related to myocardial hypertrophy after deduplication were collected. The drug-disease network showed the relationship between hirudin, myocardial hypertrophy, and the targets. Further, systematic analysis from the PPI network indicated that blood coagulation, vesicle lumen, and signaling receptor activator activity may be the potential mechanisms of hirudin in the treatment of myocardial hypertrophy, and the PI3K/AKT signaling pathway may be the most relevant to the therapeutic effect of hirudin. Then, three therapeutic targets that were highly related to myocardial hypertrophy were extracted. Hirudin can be highly bound to STAT3, IL-6, and MAPK1 and found by molecular docking, which may be the basis for its inhibitory effect on myocardial hypertrophy. In addition, in vitro experiments showed that hirudin could inhibit AngII-induced hypertrophy and death of H9c2 cells, and significantly reduce the mRNA and protein expression levels of STAT3, MAPK1, and IL-6. The above conclusions were verified in primary rat cardiomyocytes. Conclusion: Hirudin can be used to treat myocardial hypertrophy through a complex mechanism. The application of network pharmacology and experimental validation can promote the application of hirudin in cardiovascular diseases and the interpretation and understanding of molecular biological mechanisms.

7.
Brain Behav ; : e2680, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35833267

RESUMO

INTRODUCTION: Alzheimer's disease (AD), a common form of dementia, has been reported to influence 27 million individuals globally. Several risk factors including oxidative stress, gut microbiota imbalance, and cognitive activity are reported to be closely associated with the initiation or progression of AD. Although miR-483-3p was identified to be downregulated in AD patient serum. However, the biological role and mechanism of miR-483-3p remained unknown in AD. Here, we explored the role of miR-483-3p in AD. METHODS: Sprague-Dawley rats were injected with homocysteine (Hcy) to establish an AD animal model. The Morris water maze tests and contextual fear tests were conducted to assess the cognitive and memory abilities of rats. TUNEL staining was utilized to determine cell apoptosis. Luciferase reporter assay was used to evaluate the binding relation between miR-483-3p and exportin 1 (XPO1). RESULTS: Homocysteine treatment (400 µg/kg) induced the learning, cognitive and memory defects of rats. miR-483-3p was downregulated in Hcy-treated rat hippocampus. Functionally, miR-483-3p alleviated cell apoptosis and impairments of learning and memory abilities in Hcy-treated rats. In addition, miR-483-3p inhibited cell apoptosis and protein level of AD-associated factors (APP, BACE1, and Aß1-42) in PC12 cells. In mechanism, miR-483-3p was confirmed to target XPO1 in PC12 cells. XPO1 displayed high level in rat hippocampus and was negatively correlated with miR-483-3p levels. Finally, XPO1 overexpression rescued the suppressive effect of miR-483-3p on cell apoptosis and protein levels of AD-associated factors. CONCLUSIONS: miR-483-3p alleviates neural cell apoptosis and impairments of learning and memory abilities by targeting XPO1 in AD.

8.
IEEE Access ; 10: 63754-63781, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873900

RESUMO

For many machine learning tasks, deep learning greatly outperforms all other existing learning algorithms. However, constructing a deep learning model on a big data set often takes days or months. During this long process, it is preferable to provide a progress indicator that keeps predicting the model construction time left and the percentage of model construction work done. Recently, we developed the first method to do this that permits early stopping. That method revises its predicted model construction cost using information gathered at the validation points, where the model's error rate is computed on the validation set. Due to the sparsity of validation points, the resulting progress indicators often have a long delay in gathering information from enough validation points and obtaining relatively accurate progress estimates. In this paper, we propose a new progress indication method to overcome this shortcoming by judiciously inserting extra validation points between the original validation points. We implemented this new method in TensorFlow. Our experiments show that compared with using our prior method, using this new method reduces the progress indicator's prediction error of the model construction time left by 57.5% on average. Also, with a low overhead, this new method enables us to obtain relatively accurate progress estimates faster.

9.
Anim Biotechnol ; : 1-6, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35904284

RESUMO

N6-methyladenosine (m6A), the most abundant internal mRNA modification in eukaryotes, plays a vital role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Our previous study found that ADRB1 gene has m6A modification in both muscle and fat tissue. In this study, we interfered with FTO and ADRB1 genes After we cultured rabbit preadipocytes respectively. Oil red O staining and triglyceride assay were used to detect adipocyte differentiation. RT-qPCR was used to detect gene expression level and MeRIP-qPCR was used to detect the m6A modification level of gene. The results showed that FTO promoted the differentiation of adipocytes. At the same time, FTO up regulated the expression of ADRB1 gene and down regulated the m6A modification level of ADRB1 gene. Finally, we found that ADRB1 inhibited adipocyte differentiation. Together, we showed that FTO promoted adipocyte differentiation by regulating ADRB1 gene through m6A modification.

10.
Proc Natl Acad Sci U S A ; 119(30): e2201168119, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858425

RESUMO

Mitochondrial remodeling during the peri-implantation stage is the hallmark event essential for normal embryogenesis. Among the changes, enhanced oxidative phosphorylation is critical for supporting high energy demands of postimplantation embryos, but increases mitochondrial oxidative stress, which in turn threatens mitochondrial DNA (mtDNA) stability. However, how mitochondria protect their own histone-lacking mtDNA, during this stage remains unclear. Concurrently, the mitochondrial genome gain DNA methylation by this stage. Its spatiotemporal coincidence with enhanced mitochondrial stress led us to ask if mtDNA methylation has a role in maintaining mitochondrial genome stability. Herein, we report that mitochondrial genome undergoes de novo mtDNA methylation that can protect mtDNA against enhanced oxidative damage during the peri-implantation window. Mitochondrial genome gains extensive mtDNA methylation during transition from blastocysts to postimplantation embryos, thus establishing relatively hypermethylated mtDNA from hypomethylated state in blastocysts. Mechanistic study revealed that DNA methyltransferase 3A (DNMT3A) and DNMT3B enter mitochondria during this process and bind to mtDNA, via their unique mitochondrial targeting sequences. Importantly, loss- and gain-of-function analyses indicated that DNMT3A and DNMT3B are responsible for catalyzing de novo mtDNA methylation, in a synergistic manner. Finally, we proved, in vivo and in vitro, that increased mtDNA methylation functions to protect mitochondrial genome against mtDNA damage induced by increased mitochondrial oxidative stress. Together, we reveal mtDNA methylation dynamics and its underlying mechanism during the critical developmental window. We also provide the functional link between mitochondrial epigenetic remodeling and metabolic changes, which reveals a role for nuclear-mitochondrial crosstalk in establishing mitoepigenetics and maintaining mitochondrial homeostasis.


Assuntos
Metilação de DNA , DNA Mitocondrial , Implantação do Embrião , Genoma Mitocondrial , Estresse Oxidativo , Animais , Blastocisto/enzimologia , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A/genética , DNA Metiltransferase 3A/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Implantação do Embrião/genética , Mutação com Ganho de Função , Mutação com Perda de Função , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Estresse Oxidativo/genética
11.
Bioresour Technol ; 361: 127677, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35878768

RESUMO

The resource utilization of food waste is crucial, and single-cell protein (SCP) is attracting much attention due to its high value. This study aimed to convert food waste to SCP by Yarrowia lipolytica. It was found the chemical oxygen demand (COD) removal rate 77 ± 1.70% was achieved at 30 g COD/L with the protein content of biomass only 24.1 ± 0.4% w/w biomass dry weight (BDW) in one-stage fermentation system. However, the protein content was significantly increased to 38.8 ± 0.2% w/w BDW with the COD removal rate 85.5 ± 0.7% by a two-stage fermentation process, where the food waste was firstly anaerobically fermented to volatile fatty acids and then converted to SCP with Yarrowia lipolytica. Transcriptomic analysis showed that the expression of SCP-producing genes including ATP citrate (pro-S)-lyase and fumarate hydratase class II were up-regulated in the two-stage transformation, resulting in more organic degradation for SCP synthesis.

12.
Transl Vis Sci Technol ; 11(2): 40, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703567

RESUMO

Purpose: The purpose of this study was to evaluate the potential feasibility of using a smartphone app in myopia screening. Methods: The app estimates myopic refractive error by measuring the far point distance for reading three 20/20 Tumbling E letters. In total, 113 myopic subjects with astigmatism no greater than -1.75 diopters (D) were enrolled from 5 sites. The mean age was 22 ± 8.5 years. The app measurement was compared with noncycloplegic subjective refraction measurement or autorefractor if subjective refraction was not available. In addition, 22 subjects were tested with the app for repeatability. Results: For 201 eyes included, the range of spherical equivalent refraction error was 0 to -10.2 D. The app measurement and clinical measurement was highly correlated (Pearson R = 0.91, P < 0.001). There was a small bias (0.17 D) in the app measurement overall, and it was significantly different across the 5 sites due to different age of subjects enrolled at those sites (P = 0.001) - young adults in their 20s were underestimated the most by 0.49 D, whereas children were overestimated by 0.29 D. The mean absolute deviation of the app measurement was 0.65 D. The repeatability of multiple testing in terms of 95% limit of agreement was ±0.61 D. Conclusions: Overall, the app measurement is consistent with clinical measurement performed by vision care professionals. The repeatability is comparable with that of some autorefractors. Age-associated human factors may influence the app measurement. Translational Relevance: The app could be potentially used as a mass screening tool for myopia.


Assuntos
Aplicativos Móveis , Miopia , Erros de Refração , Adolescente , Adulto , Criança , Humanos , Miopia/diagnóstico , Refração Ocular , Erros de Refração/diagnóstico , Testes Visuais , Adulto Jovem
13.
Foods ; 11(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35681299

RESUMO

N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in eukaryotes. The M6A modification plays an important role in transcription and cell function. The mechanism by which m6A modification regulates meat quality remains elusive. In this study, gene knockout and overexpression were used to explore m6A-modified regulation of meat quality. The content of PCK2 in blood increased significantly with the increase of Rex rabbits' age. PCK2 expression levels in the longissimus lumborum and liver also increased significantly with the increase of Rex rabbits' age. However, the expression level of PCK2 showed no significant difference in adipose tissue. In cell experiments, we found that METTL3 inhibited adipocyte differentiation by targeting the PCK2 gene via the recognition function of YTHDF2. Finally, the results of correlation analysis showed that PCK2 expression was positively correlated with intramuscular fat, whereas PCK2 expression was negatively correlated with total water loss rate at three different stages. In addition, PCK2 expression was also negatively correlated with reduced pH value at 75 and 165 days. Intramuscular fat content, pH and muscle water holding capacity are the main factors affecting the taste and flavor of muscle. Therefore, N6-methyladenosine regulated muscle quality by targeting the PCK2 gene.

14.
Eur J Histochem ; 66(3)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35726535

RESUMO

Noncoding RNAs are important for regulation of cardiac hypertrophy. The function of MALAT1 (a long noncoding mRNA), miR-181a, and HMGB2; their contribution to cardiac hypertrophy; and the regulatory relationship between them during this process remain unknown. In the present study, we treated primary cardiomyocytes with angiotensin II (Ang II) to mimic cardiac hypertrophy. MALAT1 expression was significantly downregulated in Ang II-treated cardiomyocytes compared with control cardiomyocytes. Ang II-induced cardiac hypertrophy was suppressed by overexpression of MALAT1 and promoted by genetic knockdown of MALAT1. A dual-luciferase reporter assay demonstrated that MALAT1 acted as a sponge for miR-181a and inhibited its expression during cardiac hypertrophy. Cardiac hypertrophy was suppressed by overexpression of a miR-181a inhibitor and enhanced by overexpression of a miR-181a mimic. HMGB2 was downregulated during cardiac hypertrophy and was identified as a target of miR-181a by bioinformatics analysis and a dual-luciferase reporter assay. miR-181a overexpression decreased the mRNA and protein levels of HMGB2. Rescue experiments indicated that MALAT1 overexpression reversed the effect of miR-181a on HMGB2 expression. In summary, the results of the present study show that MALAT1 acts as a sponge for miR-181a and thereby regulates expression of HMGB2 and development of cardiac hypertrophy. The novel MALAT1/miR-181a/HMGB2 axis might play a crucial role in cardiac hypertrophy and serve as a new therapeutic target.


Assuntos
Proteína HMGB2 , MicroRNAs , Miócitos Cardíacos , RNA Longo não Codificante , Cardiomegalia/genética , Cardiomegalia/metabolismo , Células Cultivadas , Proteína HMGB2/genética , Proteína HMGB2/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo
15.
Endocr Connect ; 11(7)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35686717

RESUMO

Background: In recent decades, with the development of the global economy and the improvement of living standards, insulin resistance (IR) has become a common phenomenon. Current studies have shown that IR varies between races. Therefore, it is necessary to develop individual prediction models for each country. The purpose of this study was to develop a predictive model of IR applicable to the US population. Method: In total, 11 cycles of data from the NHANES database were selected for this study. Of these, participants from 1999 to 2010 (n = 14931) were used to establish the model, and participants from 2011 to 2020 (n = 13,646) were used to validate the model. Univariate and multivariable logistic regression was used to analyze the factors associated with IR. Optimal subset regression was used to filter the best modeling variables. ROC curves, calibration curves, and decision curve analysis were used to determine the strengths and weaknesses of the model. Results: After screening the variables by optimal subset regression, variables with covariance were excluded, and a total of seven factors (including HDL, LDL, ALB, GLB, GLU, BMI, and waist) were finally included to establish the prediction model. The AUCs were 0.851 and 0.857 in the training and validation sets, respectively, and the Brier value of the calibration curve was 0.153. Conclusion: The optimal subset predictive model proposed in this study has a great performance in predicting IR, and the decision curve analysis shows that it has a high net clinical benefit, which can help clinicians and epidemiologists easily detect IR and take appropriate interventions as early as possible.

16.
Water Res ; 221: 118744, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35728495

RESUMO

Waste activated sludge (WAS) contains high concentrations of microplastics (MPs), which could serve as vectors of various organic pollutants and heavy metals, causing synergistic transportation and pollution. The application of combined hydrothermal pretreatment (HTP) and anaerobic digestion (AD) has raised growing concerns since the low-temperature hydrothermal treatment could enhance the biogas production of WAS. However, the changes in physicochemical properties, adsorption performances, and effects on AD of MPs by HTP have not been studied. The study used three typical MPs in WAS, and it was found that the HTP (170°C & 30min) increased MPs' specific surface area and carbonyl index (CI) while decreasing the relative crystallinity. The adsorption capacity to Cd increased through the carbonylation for polyethylene microplastic (PE-MP) and polystyrene microplastic (PS-MP) while decreasing by the dechlorination for polyvinyl chloride microplastic (PVC-MP). Meanwhile, increased hydrophilicity reduced the adsorption capacities of all three typical MPs for ofloxacin. The above results indicated that the HTP could be worth blocking the adsorption of polar MPs for polar pollutants. For the pristine MPs, only PVC-MP at the highest concentration (0.5 g kg-1 VS) significantly (p < 0.05) reduced methane production by 16.2 ± 3.3% of WAS without the HTP. However, the HTP resulted in significant (p < 0.05) inhibition of methane production of WAS at high concentrations of PE-MP and PVC-MP (e.g., 0.1 and 0.5 g kg-1 VS), which was due to the acceleration of the released toxic plastic additives (dibutyl phthalate, dimethyl phthalate, and bisphenol-A). Microbial analysis showed the abundances of vital anaerobes, such as acid-producing bacteria (Acetoanerrobium and Mesotoga), proteolytic bacteria (Proteiniborus), and methanogens (Methanosaeta) clearly decreased with the PE-MP and PVC-MP after the HTP, which might result in the decreased methane production. The study provided deep-insight of MPs' behaviors during the combined HTP-AD process.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35722148

RESUMO

Background: Danshen Decoction comprises Salvia miltiorrhiza, Santalum album, and Amomum villosum. It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM). Methods: The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the in vitro hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms. Results: The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53. Conclusion: Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.

18.
JMIR Med Inform ; 10(6): e38220, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35675129

RESUMO

BACKGROUND: Asthma hospital visits, including emergency department visits and inpatient stays, are a significant burden on health care. To leverage preventive care more effectively in managing asthma, we previously employed machine learning and data from the University of Washington Medicine (UWM) to build the world's most accurate model to forecast which asthma patients will have asthma hospital visits during the following 12 months. OBJECTIVE: Currently, two questions remain regarding our model's performance. First, for a patient who will have asthma hospital visits in the future, how far in advance can our model make an initial identification of risk? Second, if our model erroneously predicts a patient to have asthma hospital visits at the UWM during the following 12 months, how likely will the patient have ≥1 asthma hospital visit somewhere else or ≥1 surrogate indicator of a poor outcome? This work aims to answer these two questions. METHODS: Our patient cohort included every adult asthma patient who received care at the UWM between 2011 and 2018. Using the UWM data, our model made predictions on the asthma patients in 2018. For every such patient with ≥1 asthma hospital visit at the UWM in 2019, we computed the number of days in advance that our model gave an initial warning. For every such patient erroneously predicted to have ≥1 asthma hospital visit at the UWM in 2019, we used PreManage and the UWM data to check whether the patient had ≥1 asthma hospital visit outside of the UWM in 2019 or any surrogate indicators of poor outcomes. Such surrogate indicators included a prescription for systemic corticosteroids during the following 12 months, any type of visit for asthma exacerbation during the following 12 months, and asthma hospital visits between 13 and 24 months later. RESULTS: Among the 218 asthma patients in 2018 with asthma hospital visits at the UWM in 2019, 61.9% (135/218) were given initial warnings of such visits ≥3 months ahead by our model and 84.4% (184/218) were given initial warnings ≥1 day ahead. Among the 1310 asthma patients in 2018 who were erroneously predicted to have asthma hospital visits at the UWM in 2019, 29.01% (380/1310) had asthma hospital visits outside of the UWM in 2019 or surrogate indicators of poor outcomes. CONCLUSIONS: Our model gave timely risk warnings for most asthma patients with poor outcomes. We found that 29.01% (380/1310) of asthma patients for whom our model gave false-positive predictions had asthma hospital visits somewhere else during the following 12 months or surrogate indicators of poor outcomes, and thus were reasonable candidates for preventive interventions. There is still significant room for improving our model to give more accurate and more timely risk warnings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/5039.

19.
BMC Musculoskelet Disord ; 23(1): 562, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689229

RESUMO

BACKGROUND: The aim of this retrospective monocentric study was to investigate the clinical efficacy of percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III displaced intra-articular calcaneal fractures (DIACFs). METHODS: The medical records of calcaneal fractures patients who were admitted to our department from January 2018 to January 2020 were retrospectively reviewed, and those meeting the inclusion criteria were fnally included for analysis. All patients were treated with percutaneous reduction and screw fixation, and no patients received bone grafting. The radiologic parameters evaluated included the BÖhler angle and the calcaneal height. In addition, the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, Maryland Foot Score (MFS), and visual analog scale (VAS) score were determined. RESULTS: Thirty-eight patients with Sanders Type-II and Type-III DIACFs were finally included, including 30 males and 8 females aged 21 to 61 years [(42.6 ± 9.6) years]. According to the Essex-Lopresti classification, 27 of the fractures were the tongue type, and 11 were the joint compression type. According to the Sanders classification, 27 of the fractures were type II, and 11 were type III. Immediately postoperatively, the calcaneal height had recovered to 39.8 ± 2.1 mm, the BÖhler angle had recovered from 4.2° ± 13.6° preoperatively to 27.2° ± 3.4° (P = 0.000). All patients were followed up for 18-42 months [(25.2 ± 9.5) months]. All fractures healed. No differences were found in the outcome measures six-months postoperatively (BÖhler angle, p = 0.24; calcaneal height, p = 0.82) or at final follow-up (BÖhler angle, p = 0.33; calcaneal height, p = 0.28) compared to the immediately postoperative values. At the final follow-up, the AOFAS score was 91.7 ± 7.4 points, with an excellent and good rate of 92.1%; the MFS was 90.3 ± 7.8 points, with an excellent and good rate of 92.1%; and the VAS score was 2.2 ± 1.5 points. None of the patients had incision complications, and one patient developed traumatic arthritis. CONCLUSION: Percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III DIACFs can achieve good recovery and maintenance of the BÖhler angle and calcaneal height. Moreover, it has the advantage of a low complication rate.


Assuntos
Traumatismos do Tornozelo , Calcâneo , Traumatismos do Pé , Fraturas Ósseas , Fraturas Intra-Articulares , Traumatismos do Joelho , Parafusos Ósseos , Transplante Ósseo , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Feminino , Traumatismos do Pé/diagnóstico por imagem , Traumatismos do Pé/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Fraturas Intra-Articulares/diagnóstico por imagem , Fraturas Intra-Articulares/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
20.
Front Microbiol ; 13: 877884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620098

RESUMO

Traditional Chinese medicine is one of the ancient medicines which is popular in Asian countries, among which the residue produced by the use of anti-biodegradables is endless, and causes significant adverse impacts on the environment. However, the high acidity of anti-biodegradable residues and some special biological activities make it difficult for microorganisms to survive, resulting in a very low degradation rate of lignocellulose in naturally stacked residues, which directly impedes the degradation of residues. We aimed to identify the fungal strains that efficiently biodegrade anti-biodegradable residue and see the possibility to improve the biodegradation of it and other agricultural wastes by co-cultivating these fungi. We isolated 302 fungal strains from anti-biodegradable residue to test hydrolysis ability. Finally, we found Coniochaeta sp., Fomitopsis sp., Nemania sp., Talaromyces sp., Phaeophlebiopsis sp. which inhabit the anti-biodegradable residues are capable of producing higher concentrations of extracellular enzymes. Synergistic fungal combinations (viz., Fomitopsis sp. + Phaeophlebiopsis sp.; Talaromyces sp. + Coniochaeta sp. + Fomitopsis sp.; Talaromyces sp. + Fomitopsis sp. + Piloderma sp. and Talaromyces sp. + Nemania sp. + Piloderma sp.) have better overall degradation effect on lignocellulose. Therefore, these fungi and their combinations have strong potential to be further developed for bioremediation and biological enzyme industrial production.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...