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1.
Med Res Rev ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515232

RESUMO

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

2.
Mol Cancer ; 23(1): 86, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685067

RESUMO

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.


Assuntos
Proteínas de Ciclo Celular , Resistencia a Medicamentos Antineoplásicos , Proteínas Nucleares , Ubiquitinação , Animais , Humanos , Camundongos , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Camundongos Knockout , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética , Modelos Animais de Doenças
3.
Adv Synth Catal ; 366(11): 2489-2494, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38895098

RESUMO

n-Bu4NI/K2S2O8 mediated transformylation from p-anisaldehyde to primary amides is reported. The mechanistic studies suggest the reaction occurs via a single electron transfer pathway. Based on the DFT electronic structure calculations of various reaction pathways, the most plausible mechanism involves the formation of a phenyl radical cation and an arenium ion as the key intermediates. It represents the first example where p-anisaldehyde is employed as a formyl source via a non-metal mediated Csp2-Csp2 bond cleavage.

4.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256202

RESUMO

Homeostatic maintenance is essential for pulp function. Disrupting pulp homeostasis may lead to pulp degeneration, such as fibrosis and calcifications. Sensory nerves constitute a crucial component of the dental pulp. However, the precise involvement of sensory nerves in pulp homeostasis remains uncertain. In this study, we observed the short-term and long-term histological changes in the dental pulp after inferior alveolar nerve transection. Additionally, we cultured primary dental pulp cells (DPCs) from the innervated and denervated groups and compared indicators of cellular senescence and cellular function. The results revealed that pulp fibrosis occurred at 2 w after the operation. Furthermore, the pulp area, as well as the height and width of the pulp cavity, showed accelerated reductions after sensory denervation. Notably, the pulp area at 16 w after the operation was comparable to that of 56 w old rats. Sensory denervation induced excessive extracellular matrix (ECM) deposition and increased predisposition to mineralization. Furthermore, sensory denervation promoted the senescence of DPCs. Denervated DPCs exhibited decelerated cell proliferation, arrest in the G2/M phase of the cell cycle, imbalance in the synthesis and degradation of ECM, and enhanced mineralization. These findings indicate that sensory nerves play an essential role in pulp homeostasis maintenance and dental pulp cell fate decisions, which may provide novel insights into the prevention of pulp degeneration.


Assuntos
Calcinose , Doenças da Polpa Dentária , Animais , Ratos , Polpa Dentária , Vias Aferentes , Homeostase , Fibrose , Denervação
5.
J Environ Manage ; 354: 120352, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367503

RESUMO

Tidal river networks are affected by the tide and influenced by complex factors related to sediment oxygen demand (SOD). In this study, we used chemical inhibition to measure the oxygen consumption of different types of SOD to explore the specific oxygen consumption mechanism of sediments. Then, we evaluated the diffusion fluxes of the sediment-water interface and factors affecting SOD using diffusive gradients in thin films. Total SOD in the tidal river network area of the Pearl River basin was ∼0.5928 g/m2/day, which was 8.47% higher than that in the non-tidal river network area but lower than that in black and odorous water reported previously. In the tidal river network area, biological SOD was 15.6% higher in summer than in winter, and the difference in total SOD was greatly influenced by human activity. We observed a significant effect of sediment on SOD in winter, whereas there were no significant correlations between sediment and SOD in summer. Different particle-size distributions lead to different organic matter contents, resulting in different biological SOD ratios between seasons. Our study found that seasonal tidal changes can affect ion exchange at the sediment water interface, leading to changes in SOD.These findings will be of great significance for the study of phenomena associated with low dissolved oxygen in tidal river networks and provide directions for future sediment pollution control.


Assuntos
Monitoramento Ambiental , Rios , Humanos , Monitoramento Ambiental/métodos , Rios/química , Sedimentos Geológicos/química , Água , Oxigênio
6.
Angew Chem Int Ed Engl ; 63(19): e202400797, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38477225

RESUMO

Traditional lithium salts are difficult to meet practical application demand of lithium metal batteries (LMBs) under high voltages and temperatures. LiPF6, as the most commonly used lithium salt, still suffers from notorious moisture sensitivity and inferior thermal stability under those conditions. Here, we synthesize a lithium salt of lithium perfluoropinacolatoborate (LiFPB) comprising highly-fluorinated and borate functional groups to address the above issues. It is demonstrated that the LiFPB shows superior thermal and electrochemical stability without any HF generation under high temperatures and voltages. In addition, the LiFPB can form a protective outer-organic and inner-inorganic rich cathode electrolyte interphase on LiCoO2 (LCO) surface. Simultaneously, the FPB- anions tend to integrate into lithium ion solvation structure to form a favorable fast-ion conductive LiBxOy based solid electrolyte interphase on lithium (Li) anode. All these fantastic features of LiFPB endow LCO (1.9 mAh cm-2)/Li metal cells excellent cycling under both high voltages and temperatures (e.g., 80 % capacity retention after 260 cycles at 60 °C and 4.45 V), and even at an extremely elevated temperature of 100 °C. This work emphasizes the important role of salt anions in determining the electrochemical performance of LMBs at both high temperature and voltage conditions.

7.
Hum Mol Genet ; 30(3-4): 182-197, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33517446

RESUMO

Lipotoxicity was recently reported in several forms of kidney disease, including focal segmental glomerulosclerosis (FSGS). Susceptibility to FSGS in African Americans is associated with the presence of genetic variants of the Apolipoprotein L1 gene (APOL1) named G1 and G2. If and how endogenous APOL1 may alter mitochondrial function by the modifying cellular lipid metabolism is unknown. Using transgenic mice expressing the APOL1 variants (G0, G1 or G2) under endogenous promoter, we show that APOL1 risk variant expression in transgenic mice does not impair kidney function at baseline. However, APOL1 G1 expression worsens proteinuria and kidney function in mice characterized by the podocyte inducible expression of nuclear factor of activated T-cells (NFAT), which we have found to cause FSGS. APOL1 G1 expression in this FSGS-model also results in increased triglyceride and cholesterol ester contents in kidney cortices, where lipid accumulation correlated with loss of renal function. In vitro, we show that the expression of endogenous APOL1 G1/G2 in human urinary podocytes is associated with increased cellular triglyceride content and is accompanied by mitochondrial dysfunction in the presence of compensatory oxidative phosphorylation (OXPHOS) complexes elevation. Our findings indicate that APOL1 risk variant expression increases the susceptibility to lipid-dependent podocyte injury, ultimately leading to mitochondrial dysfunction.


Assuntos
Apolipoproteína L1/genética , Variação Genética , Glomerulosclerose Segmentar e Focal/metabolismo , Metabolismo dos Lipídeos , Mitocôndrias/metabolismo , Podócitos/metabolismo , Negro ou Afro-Americano/genética , Animais , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/fisiopatologia , Homeostase , Humanos , Camundongos , Camundongos Transgênicos , Mitocôndrias/fisiologia , Podócitos/fisiologia , Proteinúria , Triglicerídeos/metabolismo
8.
Clin Endocrinol (Oxf) ; 98(6): 813-822, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36536522

RESUMO

OBJECTIVE: The impact of selenium (Se) on human thyroid function remains unclear, with inconsistent results from recent epidemiological studies. Moreover, the observed associations are prone to bias due to potential confounding and reverse causation. Mendelian randomization (MR) analysis facilitates the large minimization of biases produced by environmental and lifestyle influences, providing unconfounded estimates of causal effects using instrumental variables. We aim to examine the association between Se concentrations and human thyroid function using a two-sample MR analysis. DESIGN AND METHODS: Genetic instruments for Se concentrations, including toenail and blood (TAB) and blood Se concentrations, were identified from a genome-wide association study (GWAS) of blood Se (n = 5477) and toenail Se levels (n = 4162). GWAS summary statistics on thyroid phenotypes were downloaded from the ThyroidOmics consortium, including thyroid-stimulating hormone (TSH) (n = 54,288), free thyroxin (FT4) (n = 49,269), hypo (n = 53,423), and hyperthyroidism (n = 51,823). The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with the weighted median and the mode-based method. RESULTS: Genetically determined TAB Se was negatively associated with FT4 (ß = -.067; 95% confidence interval [CI] = -0.106, -0.028; p = 0.001) using the IVW analyses, as well in the additional analyses using the weighted median and weighted-mode methods. No evidence in heterogeneity, pleiotropy or outlier single-nucleotide polymorphisms was detected (all p > 0.05). Suggestive casual association between increased genetically determined TAB Se concentrations and decreased hypothyroidism risk was found by the IVW method (odds ratio [OR] = 0.847; 95% CI = 0.728, 0.985; p = 0.031). The causal effect of TAB Se on FT4 was observed in women (ß = -.076; 95% CI = -0.129, -0.024; p = 0.004). However, the influence of genetically determined higher Se concentrations on TSH levels and hyperthyroidism revealed insignificance in the primary and sensitivity analyses. CONCLUSIONS: The present MR study indicated that high Se concentration enable the decreasing of FT4 levels, and the effects of Se concentrations on FT4 remain sex-specific.


Assuntos
Hipertireoidismo , Selênio , Masculino , Humanos , Feminino , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla , Tireotropina , Polimorfismo de Nucleotídeo Único/genética
9.
Epilepsia ; 64(4): 973-985, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36695000

RESUMO

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Humanos , Eletroencefalografia , Epilepsia/patologia , Epilepsias Parciais/diagnóstico , Convulsões/patologia , Sono/fisiologia , Epilepsia Resistente a Medicamentos/diagnóstico
10.
Catheter Cardiovasc Interv ; 102(7): 1198-1209, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37937727

RESUMO

BACKGROUND: Both fractional flow reserve (FFR) and intravascular imaging (IVI) have been used to guide the decision-making for percutaneous coronary intervention (PCI) in intermediate coronary stenosis. Nevertheless, studies that directly compared the prognostic significance of these two strategies are scarce. AIMS: The aim of this meta-analyses was to evaluate the impact of FFR versus IVI to guide the decision-making in PCI for intermediate stenosis on clinical outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane, and relevant database from inception date to September 2022 for observational studies and randomized clinical trials (RCTs) which compared FFR and IVI-based decision-making in PCI for intermediate stenosis. The primary outcome was a composite of major adverse cardiac event (MACE). Pooled risk ratios (RR) were calculated using random effects models and heterogeneity were evaluated with the I2 statistic. RESULTS: We identified 5 studies (3 RCTs and 2 observational studies) with 3208 patients. The follow-up duration ranged from 12 to 24 months. Among five studies, four compared FFR with intravascular ultrasound while one compared FFR with optical coherence tomography. There was no statistically difference between FFR and IVI in the incidence of MACE (RR: 1.19; 95% confidence interval: 0.85-1.68; p = 0.31) and its individual components. These results were consistent regardless of various cut-off value of PCI across the studies. Compared with IVI, FFR was associated with a lower PCI rate (37.0% vs. 60.3%; p < 0.001). CONCLUSIONS: The decision to perform PCI for intermediate stenosis guided by FFR or IVI showed a similar clinical outcome. The use of FFR significantly reduced the need for PCI.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Humanos , Angiografia Coronária/efeitos adversos , Constrição Patológica , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia
11.
Langmuir ; 39(24): 8404-8413, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37283301

RESUMO

In this work, the strategy of immobilizing enzymes in bimetallic-organic frameworks was adopted to overcome the disadvantages of free laccases. The surface amino-silanizing of bimetallic CoCu-MOF-H hydrothermally synthesized was performed by (3-Aminopropyl)triethoxysilane (APTES). Then, glutaraldehyde was used as the cross-linking agent, laccase was covalently grafted onto CoCu-MOF-H-APTES to prepare Lac-CoCu-MOF-H-APTE. In addition, CoCu-MOF-OH also was synthesized by alkali etching of CoCu-MOF-H, and Lac-CoCu-MOF-OH-APTES composites were obtained by a similar strategy. The result showed that the relative enzyme activity of Lac-CoCu-MOF-OH-APTES exhibited 264.02% (1.8 times than that of Lac-CoCu-MOF-H-APTES) after six cycles of stability tests, while the free enzyme was almost inactivated. Moreover, the Congo red (CR) removal rate of Lac-CoCu-MOF-OH-APTES exceeded 95% within 1 h and exceeded 89.18% after six cycles at pH 3.5 and 50 °C. This work has the potential to provide a broader application prospect for CR degradation by laccase in the future.


Assuntos
Enzimas Imobilizadas , Lacase , Lacase/metabolismo , Enzimas Imobilizadas/metabolismo , Vermelho Congo , Álcalis
12.
Mol Cell Biochem ; 478(6): 1345-1359, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36309883

RESUMO

Alcohol abuse has attracted public attention and long-term alcohol exposure can lead to alcohol-featured non-ischemic dilated cardiomyopathy. However, the precise underlying mechanisms of alcoholic cardiomyopathy remain to be elucidated. This study aimed to comprehensively characterize alcohol abuse-mediated effects on downstream metabolites and genes transcription using a multi-omics strategy. We established chronic ethanol intoxication model in adult male C57BL/6 mice through 8 weeks of 95% alcohol vapor administration and performed metabolomics analysis, mRNA-seq and microRNA-seq analysis with myocardial tissues. Firstly, ethanol markedly induced ejection fraction reductions, cardiomyocyte hypertrophy, and myocardial fibrosis in mice with myocardial oxidative injury. In addition, the omics analysis identified a total of 166 differentially expressed metabolites (DEMs), 241 differentially expressed genes (DEGs) and 19 differentially expressed microRNAs (DEmiRNAs), respectively. The results highlighted that alcohol abuse mainly interfered with endogenous lipids, amino acids and nucleotides production and the relevant genes transcription in mice hearts. Based on KEGG database, the affected signaling pathways are primarily mapped to the antigen processing and presentation, regulation of actin cytoskeleton, AMPK signaling pathway, tyrosine metabolism and PPAR signaling pathway, etc. Furthermore, 9 hub genes related to oxidative stress from DEGs were selected based on function annotation, and potential alcoholic cardiotoxic oxidative stress biomarkers were determined through establishing PPI network and DEmiRNAs-DEGs cross-talk. Altogether, our data strongly supported the conclusion that ethanol abuse characteristically affected amino acid and energy metabolism, nucleotide metabolism and especially lipids metabolism in mice hearts, and underlined the values of lipids signaling and oxidative stress in the treatment strategies.


Assuntos
Alcoolismo , Etanol , Camundongos , Masculino , Animais , Etanol/toxicidade , Transcriptoma , Cardiotoxicidade , Camundongos Endogâmicos C57BL , Lipídeos
13.
Soft Matter ; 19(34): 6468-6479, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37404181

RESUMO

Microstructure adhesive pads can effectively manipulate objects in underwater environments. Current adhesive pads can achieve adhesion and separation with rigid substrates underwater; however, challenges remain in the control of adhesion and detachment of flexible materials. Additionally, underwater object manipulation necessitates considerable pre-pressure and is sensitive to water temperature fluctuations, potentially causing object damage and complicating adhesion and detachment processes. Thus, we present a novel, controllable adhesive pad inspired by the functional attributes of microwedge adhesive pads, combined with a mussel-inspired copolymer (MAPMC). In the context of underwater applications for flexible materials, the use of a microstructure adhesion pad with microwedge characteristics (MAPMCs) is a proficient approach to adhesion and detachment operations. This innovative method relies on the precise manipulation of the microwedge structure's collapse and recovery during its operation, which serves as the foundation for its efficacy in such environments. MAPMCs exhibit self-recovering elasticity, water flow interaction, and tunable underwater adhesion and detachment. Numerical simulations elucidate the synergistic effects of MAPMCs, highlighting the advantages of the microwedge structure for controllable, non-damaging adhesion and separation processes. The integration of MAPMCs into a gripping mechanism allows for the handling of diverse objects in underwater environments. Furthermore, by merging MAPMCs and a gripper within a linked system, our approach enables automatic, non-damaging adhesion, manipulation, and release of a soft jellyfish model. The experimental results indicate the potential applicability of MACMPs in underwater operations.

14.
Environ Sci Technol ; 57(48): 19395-19406, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38050814

RESUMO

Excessive nitrate in surface waters deteriorates the water quality and threatens human health. Human activities have caused increased nitrate concentrations in global surface waters over the past 50 years. An assessment of the long-term trajectory of surface-water nitrate exposure to world populations and the associated potential health risks is imperative but lacking. Here, we used global spatially explicit data on surface-water nitrate concentrations and population density, in combination with thresholds for health risks from epidemiological studies, to quantify the long-term changes in surface-water nitrate exposure to world populations at multiple spatial scales. During 1970-2010, global populations potentially affected by acute health risks associated with surface-water nitrate exposure increased from 6 to 60 million persons per year, while populations at potential chronic health risks increased from 169 to 1361 million persons per year. Potential acute risks have increasingly affected Asian countries. Populations potentially affected by chronic risks shifted from dominance by high-income countries (in Europe and North America) to middle-income countries (in Asia and Africa). To mitigate adverse health effects associated with surface-water nitrate exposure, anthropogenic nitrogen inputs to natural environments should be drastically reduced. International and national standards of maximum nitrate contamination may need to be lowered.


Assuntos
Nitratos , Poluentes Químicos da Água , Humanos , Compostos Orgânicos , Qualidade da Água , Ásia , Meio Ambiente , Poluentes Químicos da Água/análise
15.
Environ Sci Technol ; 57(36): 13506-13519, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37647507

RESUMO

Nitrous oxide (N2O) is a long-lived greenhouse gas and currently contributes ∼10% to global greenhouse warming. Studies have suggested that inland waters are a large and growing global N2O source, but whether, how, where, when, and why inland-water N2O emissions changed in the Anthropocene remains unclear. Here, we quantify global N2O formation, transport, and emission along the aquatic continuum and their changes using a spatially explicit, mechanistic, coupled biogeochemistry-hydrology model. The global inland-water N2O emission increased from 0.4 to 1.3 Tg N yr-1 during 1900-2010 due to (1) growing N2O inputs mainly from groundwater and (2) increased inland-water N2O production, largely in reservoirs. Inland waters currently contribute 7 (5-10)% to global total N2O emissions. The highest inland-water N2O emissions are typically in and downstream of reservoirs and areas with high population density and intensive agricultural activities in eastern and southern Asia, southeastern North America, and Europe. The expected continuing excessive use of nutrients, dam construction, and development of suboxic conditions in aging reservoirs imply persisting high inland-water N2O emissions.


Assuntos
Agricultura , Óxido Nitroso , Ásia Meridional , Água
16.
Acta Biochim Biophys Sin (Shanghai) ; 55(12): 1874-1883, 2023 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-37766457

RESUMO

Hyperglycemia drives dysfunction of the intestinal barrier. 5-Hydroxytryptaine 4 receptor (5-HT 4R) agonists have been considered therapeutics for constipation in clnic. However, the roles of 5-HT 4R activation in mucosa should be fully realized. Here, we investigate the effects of 5-HT 4R activation on diabetes-induced disruption of the tight junction (TJ) barrier in the colon. Not surprisingly, the TJ barrier in diabetic mice with or without 5-HT 4R is tremendously destroyed, as indicated by increased serum fluorescein isothiocyanate (FITC)-dextran and decreased transepithelial electrical resistance (TER). Simultaneously, decreased expressions of TJ proteins are shown in both wild-type (WT) and 5-HT 4R knockout (KO) mice with diabetes. Notably, chronic treatment with intraperitoneal injection of a 5-HT 4R agonist in WT mice with diabetes repairs the TJ barrier and promotes TJ protein expressions, including occludin, claudin-1 and ZO-1, in the colon, whereas a 5-HT 4R agonist does not improve TJ barrier function or TJ protein expressions in 5-HT 4R KO mice with diabetes. Furthermore, stimulation of 5-HT 4R inhibits diabetes-induced upregulation of myosin light chain kinase (MLCK), Rho-associated coiled coil protein kinase 1 (ROCK1), and phosphorylated myosin light chain (p-MLC), which are key molecules that regulate TJ integrity, in the colonic mucosa of WT mice. However, such action induced by a 5-HT 4R agonist is not observed in 5-HT 4R KO mice with diabetes. These findings indicate that 5-HT 4R activation may restore TJ integrity by inhibiting the expressions of MLCK, ROCK1 and p-MLC, improving epithelial barrier function in diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Receptores 5-HT4 de Serotonina , Animais , Camundongos , Colo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Mucosa Intestinal/metabolismo , Receptores 5-HT4 de Serotonina/genética , Receptores 5-HT4 de Serotonina/metabolismo , Serotonina/farmacologia , Serotonina/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas
17.
Ecotoxicol Environ Saf ; 251: 114509, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36621032

RESUMO

Bacillus subtilis as microbial fertilizers contribute to avoiding the harmful effects of traditional agricultural fertilizers and pesticides. However, there are many restrictions on the practical application of fertilizers. In this study, microbial biochar formulations (BCMs) were prepared by loading biochar with B. subtilis SL-44. Pot experiments were conducted to evaluate the effects of the BCMs on soil fertility, Fusarium wilt control, and radish plant growth. The application of BCMs dramatically improved soil properties and favored plant growth. Compared with SL-44 and biochar treatments, the BCMs treatments increased radish plant physical-chemical properties and activities of several enzymes in the soil. What's more, Fusarium wilt incidence had decreased by 59.88%. In addition, the BCMs treatments exhibited a significant increase in the abundance of bacterial genera in the rhizosphere soil of radish. Therefore, this study demonstrated that BCMs may be an eco-friendly strategy for improving soil fertility, reducing Fusarium wilt, and promoting radish plant growth.


Assuntos
Fusarium , Raphanus , Solo/química , Bacillus subtilis , Fertilizantes/análise , Microbiologia do Solo , Rizosfera
18.
Sensors (Basel) ; 23(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960367

RESUMO

This paper proposes a time- and event-triggered hybrid scheduling for remote state estimation with limited communication resources. A smart sensor observes a physical process and decides whether to send the local state estimate to a remote estimator via a wireless communication channel; the estimator computes the state estimate of the process according to the received data packets and the known scheduling mechanism. Based on the existing optimal time-triggered scheduling, we employ a stochastic event trigger to save precious communication chances and further improve the estimation performance. The minimum mean-squared error (MMSE) state estimate is derived since the Gaussian property is preserved. The estimation performance upper bound and communication rate are analyzed. The main results are illustrated by numerical examples.

19.
Sensors (Basel) ; 23(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36617070

RESUMO

Validation is the basis of synthetic aperture radar (SAR) image quantification applications. Based on the point target of the field site, the radiation characteristics of the backscattering coefficient image can be used to optimize the SAR imaging, and the product production system can be more closely targeted, to ensure the image product accuracy in the actual quantification application. In this study, the validation of the backscattering coefficient image was examined using calibrators, and the radiometric properties of the image were evaluated by extracting the radar cross-section of each point target. Bilinear interpolation and fast Fourier transform (FFT) interpolation methods were introduced for the local area interpolation of point targets, and the two methods were compared from the perspective of response function imaging and validation accuracy. The results show that the FFT interpolation method is more favorable for validating the backscattering coefficient.


Assuntos
Diagnóstico por Imagem , Radar , Análise de Fourier , Calibragem
20.
J Sci Food Agric ; 103(15): 7362-7373, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37394888

RESUMO

BACKGROUND: This investigation provides an important insight into Eurasian consumers' food safety beliefs and trust issues influenced by the COVID-19 pandemic. An online survey was conducted in 15 European and Asian countries involving more than 4000 consumers. RESULTS: It has confirmed that different socioeconomic characteristics, cultural aspects and education levels shape food safety perceptions within Eurasian countries. The COVID-19 pandemic influenced their beliefs and trust in food safety, which is relatively low on average. However, it is significantly higher for European consumers (especially European Union ones) compared to their Asian counterparts. Both Asian and European respondents agreed that food fraud and climate changes represent a food safety issue. However, European consumers were less concerned regarding the food safety of genetically modified foods and meat and dairy analogs/hybrids. Asian consumers were, to a greater extent, worried about the risk of getting COVID-19 from food, restaurants, food retail establishments and home food deliveries. CONCLUSION: Eurasian consumers have put their greatest extent of trust, when food safety assurance is concerned, into food scientists and food producers holding a food safety certificate. Broadly, they are uncertain to what extent their federal governments and food inspectors are competent, able and efficient in ensuring food safety. Higher education of Eurasian consumers was followed by increased food safety confidence in all parts of the food chain. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
COVID-19 , Pandemias , Humanos , COVID-19/epidemiologia , Inocuidade dos Alimentos , Carne , Inquéritos e Questionários
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