RESUMO
Staphylococcus aureus is a common pathogen found in cheese whose Staphylococcal enterotoxins (SE) are the main pathogenic factors that cause food poisoning. The objective of this study was to construct two models to evaluate the safety of Kazak cheese products in terms of composition, changes in S. aureus inoculation amount, Aw, fermentation temperature during processing, and growth of S. aureus in the fermentation stage. A total of 66 experiments comprised of five levels of inoculation amount (2.7-4 log CFU/g), five levels of Aw (0.878-0.961), and six levels of fermentation temperature (32-44 °C) were performed to confirm the growth of S. aureus and the presence of SE limit conditions. Two artificial neural networks (ANN) successfully described the relationship between the assayed conditions and the growth kinetic parameters (maximum growth rates and lag times) of the strain. The good fitting accuracy (R2 values were 0.918 and 0.976, respectively) showed that the ANN was appropriate. Experimental results showed fermentation temperature had the greatest influence on the maximum growth rate and lag time, followed by the Aw and inoculation amount. Furthermore, a probability model was built to predict the production of SE by logistic regression and neural network under the assayed conditions, which proved to be concordant in 80.8-83.8% of the cases with the observed probabilities. The maximum total number of colonies predicted by the growth model in all combinations detected with SE exceeded 5 log CFU/g. Within the range of variables, the minimum Aw for predicting SE production was 0.938, and the minimum inoculation amount for predicting SE production was 3.22 log CFU/g. Additionally, as competition between S. aureus and lactic acid bacteria (LAB) occurs in the fermentation stage, higher fermentation temperatures are conducive to the growth of LAB, which can reduce the risk of S. aureus producing SE. This study can help manufacturers to make decisions on the most appropriate production parameters for Kazak cheese products and to prevent S. aureus growth and SE production.
Assuntos
Queijo , Infecções Estafilocócicas , Humanos , Enterotoxinas , Staphylococcus aureus , Queijo/microbiologia , Microbiologia de Alimentos , ChinaRESUMO
Forest mortality and resilience driven by drought disturbances have attracted tons of attention. However, the acquisition of continuous spatial-temporal data is generally enslaved to the conventional field investigations. In this study, the resilience of semiarid forest was characterized with canopy dynamics from remote sensing observations, combining the variations in canopy greenness and water content. We integrated dense normalized difference vegetation index (NDVI) and normalized difference infrared index (NDII) time series from Landsat datasets, intending to assess the canopy resilience in 24 conifer patches along a climatic aridity gradient at the southern edge of the taiga in northern Mongolia and southern Siberia of Russia. The results exhibited four patterns of coordinated NDVI-NDII variation trends, indicating that the canopy water content of coniferous forests may decrease at first during a drought period, and sustained water loss may, in turn, induce an accompanying reduction in canopy greenness. Meanwhile, the patches with canopy recovery growth after initial declines were considered to have resilience to climate change. We further observed the combined effects of aridity degree and tree age on canopy resilience, and all seven patches with no resilience corresponded to the old-tree group (the oldest trees reached or exceeded the age of 90). The observations indicated that the old-growth forests in semiarid regions were less likely to show canopy resilience, which corresponded to a higher risk of sustained decline.
Assuntos
Secas , Taiga , Florestas , Mongólia , Federação Russa , Sibéria , ÁrvoresRESUMO
Nonstructural carbohydrates (NSCs) facilitate the adaptation of trees to drought stress. There have been a large number of studies exploring NSC changes in individual plant species and individual organ under drought and showed different trends; however, an understanding of the universal pattern of the plant NSCs responses to drought, particularly to drought duration, is still lacking. Here, we compiled data from 47 experimental studies on 52 tree species and conducted a meta-analysis to evaluate the responses of soluble sugars, starch, and TNSC (total nonstructural carbohydrates including both soluble sugars and starch) concentrations in different tree organs (leaf, stem, and root) to drought intensity and duration. We found that starch in all organs decreased and soluble sugars in leaf increased with prolonged experiment time, and the changes in soluble sugars in all organs were stronger under severe drought than under slight-to-moderate drought. Under slight-to-moderate drought, the NSC content of each organ varied with time, while with the extension of the drought duration, the NSCs gradually approached the control value (no drought stress); this trend remained in the late drought, which means that trees activated physiological regulation processes to increase carbon storage and reduce the risks of carbon starvation. In contrast, long-term severe drought could lead to a net loss of carbohydrates, especially in the root, implying that prolonged severe drought could lead to NSC depletion in the whole plant. As prolonged drought duration has occurred in and is projected for many regions, this paper could shed light into studies on how trees respond and adapt extending drought duration through nonstructural carbon production, transportation, and reallocation.
Assuntos
Secas , Árvores , Metabolismo dos Carboidratos , Carboidratos , Folhas de Planta , AmidoRESUMO
The Janus kinase (JAK) family of tyrosine kinases has been proven to provide targeted immune modulation. Orally available JAK inhibitors have been used for the treatment of immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Here, we report the design, synthesis and biological evaluation of 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl) pyrimidin-2-amino derivatives as JAK inhibitors. Systematic structure-activity relationship studies led to the discovery of compound 7j, which strongly inhibited the four isoforms of JAK kinases. Molecular modeling rationalized the importance of cyanoacetyl and phenylmorpholine moieties. The in vivo investigation indicated that compound 7j possessed favorable pharmacokinetic properties and displayed slightly better anti-inflammatory efficacy than tofacitinib at the same dosage. Accordingly, compound 7j was advanced into preclinical development.
Assuntos
Aminas/química , Anti-Inflamatórios/química , Inibidores de Janus Quinases/química , Janus Quinases/antagonistas & inibidores , Administração Oral , Aminas/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Artrite/tratamento farmacológico , Artrite/patologia , Sítios de Ligação , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Meia-Vida , Humanos , Inibidores de Janus Quinases/metabolismo , Inibidores de Janus Quinases/farmacocinética , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/metabolismo , Simulação de Acoplamento Molecular , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Pirimidinas/química , Ratos , Relação Estrutura-AtividadeRESUMO
The effects of four polyphenols-chlorogenic acid (CA), gallic acid (GA), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) on the structure, gel properties, and interaction mechanisms of myofibrillar protein (MP) were studied. The changes in MP structure with polyphenols were analyzed using circular dichroism. The ultraviolet and fluorescence spectra and thermodynamic analysis indicated that the type of binding between the four polyphenols with the MP was static quenching of complex formation. GA had a more pronounced effect on improving MP gel properties. Finally, molecular docking determined that the affinity of the protein with the four polyphenols was in the order EGCG > ECG > CA > GA, with the main interaction force being hydrophobic interactions and hydrogen bonding, but hydrogen bonding dominates the interaction between GA and the protein. The findings illuminate the mechanism of MP binding to different polyphenols and facilitate the study of polyphenol-protein properties.
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The impacts of low soil moisture (SM) and high vapour pressure deficit (VPD) on tree's photosynthesis and productivity are ultimately realized by changing water content in the canopy leaves. In this study, variations in canopy water content (CWC) that can be detected from microwave remotely sensed vegetation optical depth (VOD) have been proposed as a promising measure of vegetation water status, and we first reported that the regulation of CWC on productivity stability is universally applicable for global forests. Results of structural equation model (SEM) also confirmed the significant negative effect of CWC on coefficient of variation (CV) of productivity, indicating that the decrease in CWC could inevitably induce the instability of forest productivity under climate change. The most significant decrease (p < 0.01) of CWC is observed primarily in evergreen broadleaf forest in the tropics, implying an increasing instability of the most important carbon sink in terrestrial ecosystem.
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Ferritin, as an iron storage protein, regulates iron metabolism and delivers bioactive substances. It has been regarded as a safe, new type of natural iron supplement, with high bioavailability. In this paper, we extracted and purified ferritin from northern pike liver (NPLF). The aggregation stabilities, assemble properties, and structural changes in NPLF were investigated using electrophoresis, dynamic light scattering (DLS), circular dichroism (CD), UV-Visible absorption spectroscopy, fluorescence spectroscopy, and transmission electron microscopy (TEM) under various thermal treatments. The solubility, iron concentration, and monodispersity of NPLF all decreased as the temperature increased, and macromolecular aggregates developed. At 60 °C and 70 °C, the α-helix content of ferritin was greater. The content of α-helix were reduced to 8.10% and 1.90% at 90 °C and 100 °C, respectively, indicating the protein structure became loose and lost its self-assembly ability. Furthermore, when treated below 80 °C, NPLF maintained a complete cage-like shape, according to the microstructure. Partially unfolded structures reassembled into tiny aggregates at 80 °C. These findings suggest that mild thermal treatment (80 °C) might inhibit ferritin aggregation while leaving its self-assembly capacity unaffected. Thus, this study provides a theoretical basis for the processing and use of NPLF.
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This study aimed to investigate the effect of phosphorylation on the structure and emulsification of Coregonus peled, Esox lucius and Grass carp scale gelatin. Fourier transform infrared spectroscopy (FTIR) and endogenous fluorescence spectra showed that the structures of the three fish scale gelatins changed. Additionally, the surface hydrophobicity index of the three fish scale gelatins increased by 36.72, 31.42 and 111.67, respectively, after 1 h of phosphorylation, and the surface tension decreased by 17.27, 32.58 and 18.7 mN/m, respectively. The emulsification activity index increased by 115.86, 155.22 and 45.52 m2/g, and the emulsification stability index increased by 98.37, 256.77 and 169.61 min, respectively. The structure of fish scale gelatin changed after phosphorylation, which resulted in the improvement of emulsification. This work will provide useful information to understand the relationship between the structure and function of gelatin.
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This study aimed to investigate the effect of caspase-3 inhibitor in mitochondrial apoptosis activation on structure protein degradation during postmortem storage. Mitochondrial dysfunction, apoptotic factors, structure protein degradation and the myofibrillar rupture index between the control and caspase-3 inhibitor groups were determined. The results show caspase-3 inhibitor repressed the mitochondrial membrane permeability and mitochondrial swelling, as well as increased mitochondrial membrane potential, causing a decrease in the release of cytochrome c from mitochondria to cytoplasm and caspase-9/3 activities (P < 0.05). Subsequently, small myofibrillar proteins (desmin and troponin-T) were susceptible to degradation, initiating texture deterioration. By contrast, giant structure proteins (titin and nebulin) were degraded during later postmortem storage, predominantly contributing to fish softening. The results further suggest that caspase-3 is involved in degradation of structure proteins during postmortem through mitochondrial apoptosis pathways.
Assuntos
Esocidae , Mitocôndrias , Animais , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/metabolismo , Esocidae/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismoRESUMO
Due to the influence of climate change and extensive grazing, a large proportion of steppe grassland has been degraded worldwide. The Chinese government initiated a series of grassland restoration programs to reverse the degradation. However, the limiting factors and the restoration potential remain unknown. Here we present a process-based model to assess the restoration gap (RG) defined as maximum biomass differences between non-degraded and degraded grasslands with different degrees of soil and vegetation degradation. The process-based model Agricultural Production Systems Simulator (APSIM) was evaluated utilizing observation data from both typical and meadow steppes under natural conditions in terms of phenology, dynamics of above-ground biomass and soil water content. Scenario analysis and sensitivity analysis were subsequently performed to address the RG and controlling factors during 1969-2018. The results showed that the calibrated model performed well with r > 0.75 and model efficiency factor EF > 0.5 for all the simulation components. According to our model results, the RG was larger in typical steppe compared to that of meadow steppe and it increased with increasing soil and/or vegetation degradation, to ~60% under extremely degraded scenarios. Both soil and vegetation degradation led to reduced water use efficiency, with an elevated proportion of soil evaporation to evapotranspiration (Es/ET), however, the limiting factor for RG varied. The degradation of soil water holding capacity contributed more to RG regardless of climate conditions for typical steppe in all years and for meadow steppe in dry years. In wet years the importance of vegetation coverage reduction increased for RG in meadow steppe, where the relative importance of vegetation coverage (valued at 62.8%) was 25.6% higher than that of soil degradation. Our results demonstrated the importance of considering climate variations when developing protection and restoration programs for grassland ecosystems.
Assuntos
Ecossistema , Pradaria , Biomassa , China , Mudança Climática , SoloRESUMO
The effects of rutin (6, 30, and 150 µmol/gpro ) on the physicochemical, structural properties and gel characteristics of myofibrillar protein (MP) under oxidative stress were investigated. The addition of rutin significantly promoted the formation of oxidized MP carbonyl derivatives and dimer tyrosine, but it cannot prevent the loss of sulfhydryl groups (-SH). With increasing rutin concentration, the hydrophobic area was gradually shielded and rutin acted as a quencher to reduce the fluorescence intensity of oxidized MP. Under the oxidative stress, rutin increased the particle size and aggravated the cleavage of protein molecules. SDS-polyacrylamide gel electrophoresis revealed that rutin further aggravated oxidized MP degradation and cross-linked form polymer which cross-linked with protein to the maximum extent at 150 µmol/gpro rutin content. Moderate cross-linking between protein and rutin could improve the gel strength and water holding capacity (WHC) of oxidized MP gel. For rutin concentrations of 6 and 30 µmol/gpro , the gels had denser network structures, as observed by scanning electron microscopy. PRACTICAL APPLICATIONS: Polyphenols of the type and dosage can change the properties of the product itself and optimize the quality of product processing. Certain polyphenols may promote the oxidation process of protein-rich products, but this does not affect the improvement of product quality. The application of natural polyphenols is the promising business direction in the development of Coregonus peled industry.
Assuntos
Estresse Oxidativo , Rutina , Géis , Interações Hidrofóbicas e Hidrofílicas , Oxirredução , Rutina/farmacologiaRESUMO
Boreal forests are adapted to cold climates and are thus especially sensitive and vulnerable to climate change. In this study, we chose 10 plots covering different topographies at the southern edge of a boreal forest. The annual ring widths of the 249 Dahurican larch (Larix gmelinii) tree cores from these plots were measured and used to calculate the basal area increment (BAI) and the interannual sensitivity (Sx). We found that forests in 10 plots showed a significant change in Sx consistently around 1980. The growth of slope forest was significantly correlated with increases in temperature and precipitation, while the wetland forests, including bogs and peatland plateaus, responded negatively to temperature. In terms of precipitation, there was no effect in the peatland plateaus, but a negative effect occurred in bogs. Our results imply that the depth of the frost table could lead to different soil waterlogging from surplus water from thawing permafrost, resulting in different responses of tree growth to climate change.
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Larix , Pergelissolo , Mudança Climática , Florestas , Taiga , ÁrvoresRESUMO
The purpose of this study was to investigate the structural properties of µ-calpain induced by hydroxyl radical oxidation and its effect on the degradation of myofibrillar protein (MP) from the dorsal muscles of Coregonus peled. The carbonyl and sulfhydryl content of µ-calpain changed significantly after oxidation. The content of α-helix in the secondary structure decreased from 0.825 to 0.232 and the changes in intrinsic fluorescence and ultraviolet (UV) absorption spectra indicated that oxidation could cause the expansion and aggregation of µ-calpain molecules. Changes in µ-calpain structure could improve the activity of µ-calpain, reaching the highest value at 0.5 mM H2O2. The highest µ-calpain activity facilitate the degradation of unoxidized MP, while the degradation of oxidized MP was facilitated at the 1 mM H2O2. Thus, our results provide a scientific basis for the interaction mechanism among hydroxyl radical oxidation, µ-calpain, and MP degradation.
Assuntos
Calpaína/metabolismo , Proteínas Musculares/metabolismo , Miofibrilas/metabolismo , Proteólise , Salmonidae/metabolismo , Animais , Calpaína/química , Peróxido de Hidrogênio/metabolismo , OxirreduçãoRESUMO
This study evaluated the effects of high intensity ultrasonication (HIU, 100, 150, 200, and 250 W) and treatment time (0, 3, 6, 9, and 12 min) on the structure and emulsification properties of myofibrillar proteins (MPs) from Coregonus peled. These investigations were conducted using an ultrasonic generator at a frequency of 20 kHz (ultrasonic probe). Analysis of the carbonyl content and total number of sulfhydryl groups showed that HIU significantly improved the oxidative modification of MPs (P < 0.05). SDS-PAGE profiling showed significant degradation of the myosin heavy chain (P < 0.05). In addition, Fourier transformed infrared spectroscopy (FTIR) revealed that HIU altered these treated MP secondary structures, this was due to molecular unfolding and stretching, exposing interior hydrophobic groups. Particle size analysis showed that HIU treatment reduced particle sizes. Solubility, emulsification capacity, and emulsion stability were improved significantly, and each decreased with an increase in treatment time (up to 12 min), indicating aggregation with prolonged sonication. These results indicate that HIU could improve the emulsification properties of MPs from C. peled, demonstrating a promising method for fish protein processing.
Assuntos
Proteínas de Peixes/química , Proteínas Musculares/química , Salmonidae , Ondas Ultrassônicas , Animais , Emulsões , Interações Hidrofóbicas e HidrofílicasRESUMO
The complete mitochondrial genome of Bombyx mori strain Baiyun (Lepidoptera: Bombycidae) was determined in this study. The genome was 15,629 bp long with 37 typical animal mitochondrial genes and 1 non-coding A + T-rich region. Its gene content and order were identical to those of other lepidopteran mitochondrial genomes. All protein-coding genes (PCGs) were initiated by ATN codons except for the COI gene, which began with CGA codon. Eleven PCGs stopped with termination codon TAA, whereas the COI and COII genes ended with single T. All the tRNA genes showed typical secondary cloverleaf structures. The 496 bp AT-rich region contains several features common to other lepidopterans, such as the motif ATAGA followed by an 18-bp poly-T stretch and two microsatellite-like (TA)8 and (AT)9 elements preceded by the ATTTA motif.
Assuntos
Genoma Mitocondrial/genética , Lepidópteros/genética , Sequência Rica em At/genética , Animais , Bombyx/classificação , Bombyx/genética , Códon de Iniciação/genética , Códon de Terminação/genética , Genes Mitocondriais/genética , Lepidópteros/classificação , Fases de Leitura Aberta/genética , Análise de Sequência de DNARESUMO
An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from ß-amino acids is reported. SAR analysis revealed that bicyclic groups at the R¹ position, 3-F substituents at the R² position, and bulky aliphatic groups at the R³ position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 µM. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.
Assuntos
Aminoácidos/síntese química , Antineoplásicos/síntese química , Ácidos Borônicos/síntese química , Dipeptídeos/síntese química , Inibidores de Proteassoma , Aminoácidos/farmacocinética , Aminoácidos/farmacologia , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Ácidos Borônicos/farmacocinética , Ácidos Borônicos/farmacologia , Bortezomib , Linhagem Celular Tumoral , Dipeptídeos/farmacocinética , Dipeptídeos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Pirazinas/farmacocinética , Pirazinas/farmacologia , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A series of novel dipeptidyl boronic acid proteasome inhibitors composed of beta-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i was the most active. The IC(50) value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active as the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC(50) values nearly less than 5 microM against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in a similar way as bortezomib.
Assuntos
Aminoácidos/química , Aminoácidos/farmacologia , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Inibidores de Proteassoma , Aminoácidos/síntese química , Aminoácidos/farmacocinética , Animais , Ácidos Borônicos/síntese química , Ácidos Borônicos/farmacocinética , Linhagem Celular Tumoral , Meia-Vida , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Masculino , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacocinética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Análise de Sobrevida , Testes de Toxicidade , Peixe-ZebraRESUMO
New series of dipeptidyl boronate inhibitors of 20S proteasome were designed and synthesized. The comprehensive understanding of the SAR was obtained by utilizing the variation of four substituents. From the screened compounds in enzyme, novel inhibitors 49 and 50 were identified to be highly potent druglike candidates with IC(50) values of 1.2 and 1.6 nM, respectively, which showed better activities than the drug bortezomib on the market. Two hematologic human tumor cell lines, HL-60 and U266, were significantly sensitive to both candidates and showed nearly the same potency as the standard bortezomib with IC(50) values less than 10 nM. But as for most of the eight human solid tumor cell lines, both candidates were more potent than the standard with the IC(50) value range of 9.8-70 nM. The activity evaluation of the stereoisomers showed that changing R-isomers to S-isomers greatly reduced the potency and even induced inactivity.