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Cold stress is an adverse environmental factor that limits the growth and productivity of horticulture crops such as grapes (Vitis vinifera). In this study, we identified a grapevine cold-induced basic helix-loop-helix (bHLH) transcription factor (VvbHLH036). Overexpression and CRISPR/Cas9-mediated knockout (KO) of VvbHLH036 enhanced and decreased cold tolerance in grapevine roots, respectively. Transcriptome analysis of VvbHLH036-overexpressed roots identified threonine synthase (VvThrC1) as a potential downstream target of VvbHLH036. We confirmed that VvbHLH036 could bind the VvThrC1 promoter and activate its expression. Both the transcripts of VvThrC1 and the content of threonine were significantly induced in the leaves and roots of grapevine under cold treatment compared to controls. Conversely, these dynamics were significantly suppressed in the roots of CRISPR/Cas9-induced knockout of VvbHLH036. These observations support the regulation of threonine accumulation by VvbHLH036 through VvThrC1 during cold stress in grapevine. Furthermore, overexpression and CRISPR/Cas9-mediated knockout of VvThrC1 also confirmed its role in regulating threonine content and cold tolerance in transgenic roots at low temperature. Exogenous threonine treatment increased cold tolerance and reduced the accumulation of superoxide anions and hydrogen peroxide in grapevine leaves. Together, these findings point to the pivotal role of VvbHLH036 and VvThrC1 in the cold stress response in grapes by regulating threonine biosynthesis.
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Soluble components secreted by Tfh cells are critical for the germinal center responses. In this study, we investigated whether Tfh cells could regulate the B-cell response by releasing small extracellular vesicles (sEVs). Our results showed that Tfh cells promote B-cell differentiation and antibody production through sEVs and that CD40L plays a crucial role in Tfh-sEVs function. In addition, increased Tfh-sEVs were found in mice with collagen-induced arthritis (CIA). Adoptive transfer of Tfh cells significantly exacerbated the severity of CIA; however, the effect of Tfh cells on exacerbating the CIA process was significantly diminished after inhibiting sEVs secretion. Moreover, the levels of plasma Tfh-like-sEVs and CD40L expression on Tfh-like-sEVs in RA patients were significantly higher than those in healthy subjects. In summary, Tfh cell-derived sEVs can enhance the B-cell response, and exacerbate the procession of autoimmune arthritis.
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Artrite Experimental , Linfócitos B , Vesículas Extracelulares , Células T Auxiliares Foliculares , Animais , Artrite Experimental/imunologia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Humanos , Células T Auxiliares Foliculares/imunologia , Masculino , Artrite Reumatoide/imunologia , Diferenciação Celular/imunologia , Ativação Linfocitária/imunologia , Transferência Adotiva , Ligante de CD40/metabolismo , Ligante de CD40/imunologia , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Índice de Gravidade de Doença , FemininoRESUMO
Nitrogen (N) immobilization (Nim, including microbial N assimilation) and plant N uptake (PNU) are the two most important pathways of N retention in soils. The ratio of Nim to PNU (hereafter Nim:PNU ratio) generally reflects the degree of N limitation for plant growth in terrestrial ecosystems. However, the key factors driving the pattern of Nim:PNU ratio across global ecosystems remain unclear. Here, using a global data set of 1018 observations from 184 studies, we examined the relative importance of mycorrhizal associations, climate, plant, and soil properties on the Nim:PNU ratio across terrestrial ecosystems. Our results show that mycorrhizal fungi type (arbuscular mycorrhizal (AM) or ectomycorrhizal (EM) fungi) in combination with soil inorganic N mainly explain the global variation in the Nim:PNU ratio in terrestrial ecosystems. In AM fungi-associated ecosystems, the relationship between Nim and PNU displays a weaker negative correlation (r = -.06, p < .001), whereas there is a stronger positive correlation (r = .25, p < .001) in EM fungi-associated ecosystems. Our meta-analysis thus suggests that the AM-associated plants display a weak interaction with soil microorganisms for N absorption, while EM-associated plants cooperate with soil microorganisms. Furthermore, we find that the Nim:PNU ratio for both AM- and EM-associated ecosystems gradually converge around a stable value (13.8 ± 0.5 for AM- and 12.1 ± 1.2 for EM-associated ecosystems) under high soil inorganic N conditions. Our findings highlight the dependence of plant-microbial interaction for N absorption on both plant mycorrhizal association and soil inorganic N, with the stable convergence of the Nim:PNU ratio under high soil N conditions.
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Micorrizas , Nitrogênio , Microbiologia do Solo , Solo , Micorrizas/fisiologia , Micorrizas/metabolismo , Nitrogênio/metabolismo , Solo/química , Plantas/metabolismo , Plantas/microbiologia , EcossistemaRESUMO
Chronic inflammation is an important pathogenetic factor that leads to the progression of Alzheimer's disease (AD), and specialized pro-resolving lipid mediators (SPMs) play critical role in regulating inflammatory responses during AD pathogenesis. Maresin1 (MaR1) is the latest discovered SPMs, and it is found that MaR1 improves AD cognitive impairment by regulating neurotrophic pathways to protect AD synapses and reduce Aß production, which made MaR1 as candidate agent for AD treatment. Unfortunately, the underlying mechanisms are still largely known. In this study, the AD mice and cellular models were subjected to MaR1 treatment, and we found that MaR1 reduced Aß production to ameliorate AD-related symptoms and increased the expression levels of ADAM10/17, sAPPα and sAPPß to exert its anti-inflammatory role. In addition, as it was determined by Western Blot analysis, we observed that MaR1 could affected the neuroprotective signal pathways. Specifically, MaR1 downregulated p57NTR and upregulated TrkA to activate the p75NTR/TrkA signal pathway, and it could increase the expression levels of p-PI3K and p-Akt, and downregulated p-mTOR to activate the PI3K/AKT/ERK/mTOR pathway. Finally, we verified the role of ADAM10/17 in regulating AD progression, and we found that silencing of ADAM10/17 inactivated the above neuroprotective signal pathways to aggravate AD pathogenesis. In conclusion, MaR1 is verified as potential therapeutic agent for AD by eliminating Aß production, upregulating ADAM10/17, sAPPα and sAPPß, and activating the neuroprotective p75NTR/TrkA pathway and the PI3K/AKT/ERK/mTOR pathway.
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Proteína ADAM10 , Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides , Ácidos Docosa-Hexaenoicos , Transdução de Sinais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Animais , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Peptídeos beta-Amiloides/metabolismo , Camundongos , Inflamação/metabolismo , Projetos Piloto , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , MasculinoRESUMO
Myocardial ischemia-reperfusion injury (MIRI) poses a significant threat to patients with coronary heart disease. Adenosine A2A receptors have been known as a protective role in MIRI by regulating autophagy, so we assumed that activation of adenosine A2B receptor (A2BAR) might exert a similar effect during MIRI and underlying mechanism be related to proteostasis maintenance as well. In situ hearts were subjected to 30 min of ischemia and 120 min of reperfusion (IR), while invitro cardiomyocytes from neonatal rats experienced 6 h of oxygen-glucose deprivation followed by 12 h of reoxygenation (OGDR). Initially, we observed that post-ischemia-reperfusion induced autophagy flux blockade and ERS both in vivo and in vitro, evident through the increased expression of p62, LC3II, and BIP, which indicated the deteriorated proteostasis. We used a selective A2BAR agonist, Bay 60-6583, to explore the positive effects of A2BAR on cardiomyocytes and found that A2BAR activation rescued damaged cardiac function and morphological changes in the IR group and improved frail cell viability in the OGDR group. The A2BAR agonist also alleviated the blockage of autophagic flux, coupled with augmented ERS in the IR/OGDR group, which was reassured by using an autophagy inhibitor chloroquine (CQ) and ERS inhibitor (4-PBA) in vitro. Additionally, considering cAMP/PKA as a well-known downstream effector of A2BAR, we utilized H89, a selective PKA inhibitor. We observed that the positive efficacy of Bay 60-6583 was inhibited by H89. Collectively, our findings demonstrate that the A2BAR/cAMP/PKA signaling pathway exerts a protective role in MIRI by mitigating impaired autophagic flux and excessive ERS.
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Aminopiridinas , Isoquinolinas , Traumatismo por Reperfusão Miocárdica , Sulfonamidas , Humanos , Ratos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Receptor A2B de Adenosina/metabolismo , Miócitos Cardíacos/metabolismo , Autofagia , Isquemia/metabolismo , Estresse do Retículo Endoplasmático , ApoptoseRESUMO
This study aimed to develop an enhanced environmental dry eye (EDE) model that accurately reproduces the etiology of prolonged visual fatigue and investigates the underlying pathological features. A total of 40 adult SPF-grade Wistar rats were randomly assigned to control (n = 20) and model (n = 20) groups. Rats in the control group were maintained under normal conditions, while rats in the model group were exposed to a controlled frontal airflow of 2-4 m/s from a fan for 7.5 h daily while placed on a suspended cylindrical wire mesh frame. Various assessments were performed at different time points during the 14-day experiment, including blink frequency, tear secretion (phenol red thread test), tear film breakup time (BUT), fluorescein staining (FL), corneal epithelial status (light microscopy), ultrastructure of corneal epithelial cells (electron microscopy), and expression levels of inflammatory cytokines (IL-1ß, TNF-α) in tears (enzyme-linked immunosorbent assay). Additionally, mRNA and protein expression levels of MMP-9, IL1ß, IL6, TNF-α, IFN-γ, and caspase-3 in corneal tissues were quantified (real-time quantitative PCR and Western blotting). Compared to the control group, the model group rats exhibited significant decreases in blink frequency (P < 0.001), tear secretion (Schirmer I test) values (P < 0.001), and tear film breakup time levels (P < 0.001). There was also a significant increase in fluorescein staining scores (P < 0.001) in the model group. Histological examination revealed distinct differences of the corneal epithelium between groups. The corneal epithelium of the model group appeared thicker, with disorganized cell arrangement in the superficial and basal layers, partial defects or detachment of superficial epithelial cells, and a rough, uneven surface. Scanning electron microscopy observations showed a rough corneal epithelial surface with numerous cracks and scattered vesicular-like structures in the model group. Furthermore, the model group rats exhibited a significant increase in expression of IL-1ß and TNF-α in tears (P < 0.001), and upregulated expression levels of MMP-9, TNF-α, IL-1ß, caspase-3, IL-6, and IFN-γ at both the mRNA and protein levels in corneal tissues (P < 0.001). In conclusion, the modified "wire-meshing cylindrical board" model effectively overcomes the limitations of the traditional "jogging board " dry eye model and successfully simulates the etiology of prolonged visual fatigue. This innovative EDE model demonstrates a high degree of relevance to dry eye conditions resulting from prolonged visual tasks, with a high success rate of model induction. Moreover, it proves to be a simple, practical, and easily replicable model, making it highly suitable for further studies on prolonged visual fatigue and facilitating its widespread adoption in research and clinical applications.
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Astenopia , Síndromes do Olho Seco , Ratos , Animais , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Astenopia/metabolismo , Ratos Wistar , Síndromes do Olho Seco/metabolismo , Lágrimas/metabolismo , Fluoresceína/metabolismo , Interleucina-1beta/metabolismo , RNA Mensageiro/metabolismoRESUMO
BACKGROUND & AIMS: Many systematic reviews explore the association of non-alcoholic fatty liver disease (NAFLD) with mortality, but none of them explores sex-based differences in detail. We aimed to assess whether NAFLD is associated with cause-specific mortality, all-cause mortality, and cancer incidence in both men and women. METHODS: The PubMed, Embase, and Medline databases were searched from inception through April 2023 for eligible studies. We separately pooled relative risks (RRs) for men and women using a random effects model. Subsequently, the RRs and 95% CIs (confidence intervals) in each study were used to calculate the women-to-men ratio of RRs (RRR). Furthermore, subgroup analyses were performed to explore the robustness of outcomes. The random-effects model was employed to conduct sensitivity analyses to determine the impact of specific studies on the overall findings. RESULTS: The meta-analysis included nine cohort studies comprising 557 614 patients with NAFLD were chosen. Women were 44% more likely than men to get cancer among those with NAFLD (RRR: 1.44; 95% CI: 1.02-2.04; p = .039). However, no sex-related differences were observed between NAFLD and all-cause mortality (RRR: 1.06; 95% CI: 0.56-2.01; p = .861), liver-related mortality (RRR: 1.06; 95% CI: 0.02-69.82; p = .977), cardiovascular mortality (RRR: 1; 95% CI: 0.65-1.53; p = .987) and liver cancer (RRR: 0.76; 95% CI: 0.43-1.36; p = .36). CONCLUSIONS: There may be sex variations between NAFLD and the risk of cancer, with the connection being stronger in females than in males.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Feminino , Masculino , Fatores Sexuais , Fatores de Risco , Incidência , Causas de Morte , Neoplasias Hepáticas/mortalidadeRESUMO
Four anaerobic, Gram-stain-positive, non-motile, non-sporulating rod-shaped bacterial strains (R7T, R21, R22 and R25T) were isolated from the intestinal contents of plateau pika (Ochotona curzoniae) collected from the Qinghai-Tibet Plateau, PR China. The four isolates grew at between 25 and 42 °C (optimally at 35-37 °C), and with 0.3-3.3% NaCl (w/v) [optimum, 1.3% (w/v)]. Adding l-arginine to the medium could promote their growth. Strains R7T and R21 were most closely related to Adlercreutzia caecimuris B7T (97.48% 16S rRNA gene sequence similarity). Strains R25T and R22 were most closely related to Adlercreutzia equolifaciens DSM 19450T (98.25% 16S rRNA gene sequence similarity). The genome sequences of R7T and R25T were 2.89 and 2.90 Mb in size with 63.6 and 62.8 mol% DNA G+C contents, respectively. Phylogenetic analysis based on 16S rRNA gene sequences and core genes revealed that R7T and R21 were most closely related to A. caecimuris B7T and Adlercreutzia mucosicola DSM 19490T, whereas R25T and R22 were most closely related to A. equolifaciens DSM 19450T and Adlercreutzia rubneri ResAG-91T. R7T, R25T and the closely related species had average nucleotide identity (ANI) values of 81.9-83.2% as well as digital DNA-DNA hybridisation (dDDH) values between 27.3 and 27.9%, which clearly indicated that they represent two novel species within the genus Adlercreutzia. For R7T and R25T, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan, and the whole cell sugars included galactose, glucose and ribose. On the basis of these results, we propose that strains R7T and R25T represent two novel species of the genus Adlercreutzia, namely Adlercreutzia wanghongyangiae sp. nov. and Adlercreutzia shanghongiae sp. nov., respectively. The type strains are R7T (=GDMCC 1.4459T=KCTC 25860T) and R25T (=GDMCC 1.4458T=KCTC 25861T).
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Lagomorpha , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ácidos Graxos/química , Animais , Lagomorpha/microbiologia , China , Tibet , Hibridização de Ácido Nucleico , PeptidoglicanoRESUMO
Two novel strain pairs (HM61T/HM23 and S-34T/S-58) were isolated from soil and the faeces of Tibetan antelope (Pantholops hodgsonii) collected at the Qinghai-Tibet Plateau of PR China. All four new isolates were aerobic, non-motile, Gram-stain-positive, catalase-positive, oxidase-negative, and short rod-shaped bacteria. The results of phylogenetic analysis based on the full-length 16S rRNA genes and 283 core genomic genes indicated that the four strains were separated into two independent branches belonging to the genus Nocardioides. Strains HM61T and HM23 were most closely related to Nocardioides pelophilus THG T63T (98.58 and 98.65â% 16S rRNA gene sequence similarity). Strains S-34T and S-58 were most closely related to Nocardioides okcheonensis MMS20-HV4-12T (98.89 and 98.89â% 16S rRNA gene sequence similarity). The G+C contents of the genomic DNA of strains HM61T and S-34T were 70.6 and 72.5âmol%, respectively. Strains HM61T, S-34T and the type strains of closely related species in the analysis had average nucleotide identity values of 75.4-90.5â% as well as digital DNA-DNA hybridization values between 20.1 and 40.8â%, which clearly indicated that the four isolates represent two novel species within the genus Nocardioides. The chemotaxonomic characteristics of strains HM61T and S-34T were consistent with the genus Nocardioides. The major fatty acids of all four strains were iso-C16â:â0, C17â:â1 ω8c or C18â:â1 ω9c. For strains HM61T and S-34T, MK-8(H4) was the predominant respiratory quinone, ll-2,6-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan, and the polar lipids profiles were composed of diphosphatidylglycerol and phosphatidylglycerol. Based on phylogenetic, phenotypic, and chemotaxonomic data, we propose that strains HM61T and S-34T represent two novel species of the genus Nocardioides, respectively, with the names Nocardioides bizhenqiangii sp. nov. and Nocardioides renjunii sp. nov. The type strains are HM61T (=GDMCC 4.343T=JCM 36399T) and S-34T (=CGMCC 4.7664T=JCM 33792T).
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Antílopes , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Fezes , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Microbiologia do Solo , RNA Ribossômico 16S/genética , Tibet , Ácidos Graxos/análise , Ácidos Graxos/química , DNA Bacteriano/genética , Fezes/microbiologia , Antílopes/microbiologia , Animais , China , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Actinomycetales/classificação , Peptidoglicano , Fosfolipídeos/análiseRESUMO
Six novel bacterial strains, designated N016T, N017, N022T, N028, N056T, and N064, were isolated from soil sampled on the Qinghai-Tibet Plateau. Cells were aerobic, orange or yellow, globular or rod-shaped, non-motile, non-spore-forming, Gram-stain-positive, catalase-positive and oxidase-negative. All the isolates were salt-tolerant and could grow in the range of 4-42â°C. Results of phylogenomic analyses based on 16S rRNA gene sequences and core genomic genes showed that the three pairs of strains (N016T/N017, N022T/N028, and N056T/N064) were closely related to the members of the genus Planococcus, and clustered with Planococcus ruber, Planococcus glaciei, and Planococcus chinensis. The digital DNA-DNA hybridization and average nucleotide identity values of the six novel strains with other members of the genus Planococcus were within the ranges of 18.7-53â% and 70.58-93.49â%, respectively, all below the respective recommended thresholds of 70.0â% and 95-96â%. The genomic DNA G+C content of the six strains ranged from 43.5 to 46.0 mol%. The major fatty acids of the six strains were anteiso-C15â:â0, iso-C14â:â0, and C16â:â1 ω7c alcohol. The predominant polar lipids of strains N016T, N022T, and N056T were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Menaquinones 7 and 8 were the respiratory quinones. The results of the above analyses indicated that the six strains represent three novel species of the genus Planococcus, for which the names Planococcus shenhongbingii sp. nov. (type strain N016T=GDMCC 1.4062T=JCM 36224T), Planococcus shixiaomingii sp. nov. (type strain N022T=GDMCC 1.4063T=JCM 36225T), and Planococcus liqunii sp. nov. (type strain N056T=GDMCC 1.4064T=JCM 36226T) are proposed.
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Hibridização de Ácido Nucleico , Filogenia , Planococcus (Bactéria) , RNA Ribossômico 16S , Análise de Sequência de DNA , Microbiologia do Solo , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ácidos Graxos/análise , Tibet , Planococcus (Bactéria)/genética , Planococcus (Bactéria)/isolamento & purificação , Planococcus (Bactéria)/classificação , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Fosfolipídeos/análiseRESUMO
BACKGROUND: Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities. RESULTS: In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14-C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14-C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities. CONCLUSION: This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure-activity relationships of surfactin and other lipopeptide compounds.
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Ácidos Graxos , Tensoativos , Ácidos Graxos/metabolismo , Tensoativos/metabolismo , Ácido Glutâmico/metabolismo , Lipopeptídeos , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Peptídeos Cíclicos/química , Bacillus subtilis/genéticaRESUMO
Flexible solid-state zinc-air batteries as a wearable energy storage device with great potential, and their separators, which control ion permeability, inhibit zinc dendrite generation, and regulate catalytic active sites, have been developed as gel electrolyte separators with high retention of electrolyte uptake. However, the gel electrolyte separator still has problems such as poor affinity with the electrolyte and poor ionic conductivity, which limits its further application. In order to further improve the electrolyte absorption, ionic conductivity and mechanical strength of cellulose acetate(CA)/polyvinyl alcohol (PVA) nanofibers, TiO2was added to CA/PVA to increase the porosity, and glutaraldehyde (GA) was used to modify the CA/PVA/TiO2separator by acetal reaction with CA and PVA to make the molecules closely linked. The results shows that the optimal mass fractions of TiO2and GA were 2% and 5%, respectively. At this time, the porosity and absorption rate of the separator increased from 48% to 68.2% and 142.4% to 285.3%, respectively. The discharge capacity reached 179 mA cm-3, and the cycle stability rate was 89% after 7 stable constant current charge/discharge cycles.
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Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.
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Biomarcadores , Doença da Artéria Coronariana , Proteínas de Membrana , Análise da Randomização Mendeliana , Proteômica , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Aterosclerose/sangue , Aterosclerose/genética , Biomarcadores/sangue , Estudos de Casos e Controles , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/sangueRESUMO
BACKGROUND: Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. METHODS: An analysis of a prospective cohort from the 2007-2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. RESULTS: Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17-1.81) and CVD (HR, 1.79; 95% CI, 1.21-2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54-0.84) and CVD (HR, 0.46; 95% CI, 0.30-0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25-1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. CONCLUSIONS: This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.
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Doenças Cardiovasculares , Adulto , Humanos , Café , Inquéritos Nutricionais , Estudos Prospectivos , Postura Sentada , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: This study aims to comprehensively verify the efficacy of Buyang Huanwu Decoction in improving cognitive function in patients with diabetes. METHODS: Patients clinically diagnosed with mild cognitive impairment (MCI) assigned to either the placebo group or the Buyang Huanwu Decoction group. After strict screening and exclusions, a total of 156 participants completed the clinical trial, with 76 in the placebo group and 80 in the Buyang Huanwu Decoction group. RESULTS: After treatment, Buyang Huanwu Decoction group showed higher Mini-Mental State Examination and Montreal Cognitive Assessment scores compared to placebo (p < 0.05). Memory and Executive Screening, Boston Naming Test, and Animal Fluency Test scores were also higher in the treatment group (p < 0.05). No significant differences were found in DST and CDT scores (p > 0.05). Trail Making Test scores were lower in the treatment group (p < 0.05). No significant difference was observed between the two groups in terms of complications (p > 0.05). CONCLUSION: Patients receiving Buyang Huanwu Decoction treatment demonstrated improvement in cognitive function, showing positive effects and providing preliminary evidence for the role of Buyang Huanwu Decoction in improving cognitive function in patients with diabetes. This suggests its potential for clinical application and further promotion.
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Bearings are crucial components of machinery and equipment, and it is essential to inspect them thoroughly to ensure a high pass rate. Currently, bearing scratch detection is primarily carried out manually, which cannot meet industrial demands. This study presents research on the detection of bearing surface scratches. An improved YOLOV5 network, named YOLOV5-CDG, is proposed for detecting bearing surface defects using scratch images as targets. The YOLOV5-CDG model is based on the YOLOV5 network model with the addition of a Coordinate Attention (CA) mechanism module, fusion of Deformable Convolutional Networks (DCNs), and a combination with the GhostNet lightweight network. To achieve bearing surface scratch detection, a machine vision-based bearing surface scratch sensor system is established, and a self-made bearing surface scratch dataset is produced as the basis. The scratch detection final Average Precision (AP) value is 97%, which is 3.4% higher than that of YOLOV5. Additionally, the model has an accuracy of 99.46% for detecting defective and qualified products. The average detection time per image is 263.4 ms on the CPU device and 12.2 ms on the GPU device, demonstrating excellent performance in terms of both speed and accuracy. Furthermore, this study analyzes and compares the detection results of various models, demonstrating that the proposed method satisfies the requirements for detecting scratches on bearing surfaces in industrial settings.
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The combined process of biochar (BC) and potassium ferrate (PF) offers a fascinating technique for efficient dewatering of digestate. However, the effects of BC/PF treatment on the dewaterability and mechanisms of FWD are still unknown. This study aimed to reveal the impact mechanisms of BC/PF treatment on digestate dewatering performance. Experimental results indicated that BC/PF treatment significantly enhanced the dewaterability of digestate, with the minimum specific resistance to filtration of (1.05 ± 0.02) × 1015 m·kg-1 and water content of 57.52 ± 0.51% being obtained at the concentrations of 0.018 g·g-1 total solid (TS) BC300 and 0.20 g·g-1 TS PF, which were 8.60% and 13.59% lower than PF treatment, respectively. BC/PF treatment proficiently reduced the fractal dimension, bound water content, apparent viscosity, and gel-like network structure strength of digestate, as well as increased the floc size and zeta potential of digestate. BC/PF treatment promoted the conversion of extracellular polymeric substances (EPS) fractions from inner EPS to soluble EPS, increased the fluorescence intensity of the dissolved compounds, and enhanced the hydrophobicity of proteins. Mechanisms investigations showed that BC/PF enhanced dewatering through non-reactive oxygen species pathways, i.e., via strong oxidative intermediate irons species Fe(V)/Fe(IV). BC/PF treatment enhanced the solubilization of nutrients, the inactivation of fecal coliforms, and the mitigation of heavy metal toxicity. The results suggested that BC/PF treatment is an effective digestate dewatering technology which can provide technological supports to the closed-loop treatment of FWD.
Assuntos
Carvão Vegetal , Perda e Desperdício de Alimentos , Compostos de Ferro , Ferro , Compostos de Potássio , Eliminação de Resíduos , Alimentos , Esgotos/química , Água/química , Eliminação de Resíduos Líquidos/métodosRESUMO
This paper develops a thermodynamic entropy-based life prediction model to estimate the low-cycle fatigue (LCF) life of the nickel-based superalloy GH4169 at elevated temperature (650 °C). The gauge section of the specimen was chosen as the thermodynamic system for modeling entropy generation within the framework of the Chaboche viscoplasticity constitutive theory. Furthermore, an explicitly numerical integration algorithm was compiled to calculate the cyclic stress-strain responses and thermodynamic entropy generation for establishing the framework for fatigue life assessment. A thermodynamic entropy-based life prediction model is proposed with a damage parameter based on entropy generation considering the influence of loading ratio. Fatigue lives for GH4169 at 650 °C under various loading conditions were estimated utilizing the proposed model, and the results showed good consistency with the experimental results. Finally, compared to the existing classical models, such as Manson-Coffin, Ostergren, Walker strain, and SWT, the thermodynamic entropy-based life prediction model provided significantly better life prediction results.
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Shifts in plant phenology influence ecosystem structures and functions, yet how multiple global change drivers interact to affect phenology remains elusive. We conducted a meta-analysis of 242 published articles to assess interactions between warming (W) and other global change drivers including nitrogen addition (N), increased precipitation (IP), decreased precipitation (DP) and elevated CO2 (eCO2 ) on multiple phenophases in experimental studies. We show that leaf out and first flowering were most strongly affected by warming, while warming and decreased precipitation were the most pronounced drivers for leaf colouring. Moreover, interactions between warming and other global change drivers were common and both synergistic and antagonistic interactions were observed: interactions W + IP and W + eCO2 were frequently synergistic, whereas interactions W + N and W + DP were mostly antagonistic. These findings demonstrate that global change drivers often affect plant phenology interactively. Incorporating the multitude of interactions into models is crucial for accurately predicting plant responses to global changes.
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Clima , Ecossistema , Plantas , Folhas de Planta/fisiologia , Reprodução , Mudança ClimáticaRESUMO
BACKGROUND: Abscisic acid (ABA) receptor pyrabactin resistance 1/PYR1-like/regulatory components of ABA receptor proteins (PYR/PYL/RCARs) have been demonstrated to play pivotal roles in ABA signaling and in response to diverse environmental stimuli including drought, salinity and osmotic stress in Arabidopsis. However, whether and how GhPYL9-5D and GhPYR1-3A, the homologues of Arabidopsis PYL9 and PYR1 in cotton, function in responding to ABA and abiotic stresses are still unclear. RESULTS: GhPYL9-5D and GhPYR1-3A were targeted to the cytoplasm and nucleus. Overexpression of GhPYL9-5D and GhPYR1-3A in Arabidopsis wild type and sextuple mutant pyr1pyl1pyl2pyl4pyl5pyl8 plants resulted in ABA hypersensitivity in terms of seed germination, root growth and stomatal closure, as well as seedling tolerance to water deficit, salt and osmotic stress. Moreover, the VIGS (Virus-induced gene silencing) cotton plants, in which GhPYL9-5D or GhPYR1-3A were knocked down, showed clearly reduced tolerance to polyethylene glycol 6000 (PEG)-induced drought, salinity and osmotic stresses compared with the controls. Additionally, transcriptomic data revealed that GhPYL9-5D was highly expressed in the root, and GhPYR1-3A was strongly expressed in the fiber and stem. GhPYL9-5D, GhPYR1-3A and their homologs in cotton were highly expressed after treatment with PEG or NaCl, and the two genes were co-expressed with redox signaling components, transcription factors and auxin signal components. These results suggest that GhPYL9-5D and GhPYR1-3A may serve important roles through interplaying with hormone and other signaling components in cotton adaptation to salt or osmotic stress. CONCLUSIONS: GhPYL9-5D and GhPYR1-3A positively regulate ABA-mediated seed germination, primary root growth and stomatal closure, as well as tolerance to drought, salt and osmotic stresses likely through affecting the expression of multiple downstream stress-associated genes in Arabidopsis and cotton.